Biomedical subjects

W J Peacock

Publications and source records attributed to W J Peacock.

At least 37 records · Page 2Linked to original sources

PubMed1999

A TM3-like MADS-box gene from Eucalyptus expressed in both vegetative and reproductive tissues.

MADS-box genes in plants are a diverse class of transcription factors that are involved in regulating developmental processes, particularly meristem and organ identity during floral development. They are characterized by a highly conserved MADS-box domain of 59 amino acids that binds to specific DNA sequences. We report the characterization of a cDNA clone, ETL (Eucalyptus TM3 Like), from Eucalyptus globulus subspecies bicostata encoding a putative transcription factor of the MADS-box class that is strongly expressed in both vegetative and floral tissues, suggesting that it regulates processes other than floral development. The clone was isolated from a floral bud cDNA library with a probe generated from Eucalyptus genomic DNA by PCR using degenerate primers to the MADS-box of the floral regulatory gene APETALA 1. The ETL cDNA clone encodes a putative protein of 206 amino acids that contains an N-terminal MADS-box and a helical domain of approx. 60 amino acids predicted to form a coiled-coil (K-box). These structural features are characteristic of plant MADS-box proteins. The MADS-box domain contains all the signature residues of a class of MADS-box genes typified by the tomato gene TM3 and overall, ETL shows 56% amino acid identity to TM3. Like TM3, the ETL gene is expressed in both vegetative and reproductive organs, predominantly in root and shoot meristems and organ primordia, as well as in developing male and female floral organs.

Amino Acid Sequence↗

PubMed1999

Genes controlling fertilization-independent seed development in Arabidopsis thaliana.

We have cloned two genes, FIS1 and FIS2, that control both fertilization independent seed development and postpollination embryo development in Arabidopsis. These genes confer female gametophytic phenotypes. FIS2 encodes a protein with a C2H2 zinc-finger motif and three putative nuclear localization signals, indicating that it is likely to be a transcription factor. FIS1 encodes a protein with homology to the Drosophila Polycomb group gene Enhancer-of-zeste and is identical to the recently described Arabidopsis gene MEDEA. FIS1 is a protein with a number of putative functional domains, including the SET domain present in Enhancer-of-zeste-related proteins. Comparison of the position of the lesions in the fis1 and medea mutant alleles indicates that fis1 is a null allele producing a truncated polypeptide lacking all the protein domains whereas the deduced protein from medea lacks only the SET domain. We present a model of the role of FIS1 and FIS2 gene products in seed development.

Alleles↗

PubMed1999

Beneficial effect of siphoning in treatment of adult hydrocephalus.

OBJECTIVE: To increase awareness about the treatment of adult patients with shunt-nonresponsive hydrocephalus--a state characterized by marked ventriculomegaly, low intracranial pressure, and a patent cerebrospinal fluid diversionary shunt. DESIGN: Retrospective analysis of hospital and outpatient records. PATIENTS: Four patients with symptomatic ventriculomegaly and patent ventriculoperitoneal shunts treated with a protocol of progressive ventricular hypotension induced by external cerebrospinal fluid drainage. RESULTS: Severe clinical manifestations exhibited by the patients, including parkinsonian features, Parinaud syndrome, and extensor posturing, completely reversed once a normalization of ventricular size was achieved. External ventricular drainage pressures as low as -30 cm H2O were required to reduce ventricular size. All patients finally received a shunt incorporating a standard medium differential pressure valve with no antisiphon device. CONCLUSIONS: Shunt siphoning may be an essential mechanism by which cerebrospinal fluid shunting is effective in many patients with adult hydrocephalus. Cerebrospinal fluid shunts that contain an antisiphon device are ineffective in these patients, despite the attainment of "physiologic" intracranial pressures. Based on reported experimental and clinical evidence, it seems that the cause of this condition may be related to abnormally high intracranial compliance.

Adult↗

PubMed1999

Fetal neurenteric cyst causing hydrops: case report and review of the literature.

Routine prenatal ultrasound revealed a unilocular cystic mass associated with upper thoracic hemivertebrae that grew to 6 cm at 28 weeks and was associated with hydrops. A thoraco-amniotic shunt decompressed the cyst and resolved the hydrops, but the shunt occluded 17 days later. Preterm labour led to vaginal delivery at 31 2/7 weeks. Postnatally, the cyst was decompressed by thoracentesis due to respiratory distress. It was resected on day four of life. Severe tracheobronchomalacia was present post-operatively, presumably due to prenatal mass effect of the cyst. At one year of age, the child has recovered completely without adverse respiratory or neurological sequelae.

Adult↗

PubMed1999

Multiple DNA methyltransferase genes in Arabidopsis thaliana.

Methylation of plant DNA occurs at cytosines in any sequence context, and as the Arabidopsis methyltransferase, METI, preferentially methylates cytosines in CG dinucleotides, it is likely that Arabidopsis has other methyltransferases with different target specificities. We have identified five additional genes encoding putative DNA methyltransferases. Three of these genes are very similar to METI throughout the coding region; these genes probably arose by a series of gene duplication events, the most recent giving rise to METIIa and METIIb. METIIa and b are expressed at low levels in vegetative and floral organs and the level of transcripts is not affected by the introduction of a METI antisense transgene, nor do the METII enzymes substitute for the reduced activity of METI in methylating CG dinucleotides. METIII is not essential as it encodes a truncated protein. Two other genes encode a second class of DNA methyltransferase with the conserved motifs characteristic of cytosine methyltransferases, but with little homology to the METI-like methyltransferases through the remainder of the protein. These two methyltransferases are characterized by the presence of a chromodomain inserted within the methyltransferase domain, suggesting that they may be associated with heterochromatin. Both these genes are transcribed at low levels in vegetative and reproductive tissues.

Arabidopsis↗

PubMed1999

Arabidopsis roots and shoots have different mechanisms for hypoxic stress tolerance.

Arabidopsis has inducible responses for tolerance of O2 deficiency. Plants previously exposed to 5% O2 were more tolerant than the controls to hypoxic stress (0.1% O2 for 48 h) in both roots and shoots, but hypoxic acclimation did not improve tolerance to anoxia (0% O2). The acclimation of shoots was not dependent on the roots: increased shoot tolerance was observed when the roots of the plants were removed. An adh (alcohol dehydrogenase) null mutant did not show acclimation of the roots but retained the shoot survival response. Abscisic acid treatment also differentiated the root and shoot responses; pretreatment induced root survival in hypoxic stress conditions (0.1% O2) but did not induce any increase in the survival of shoots. Cycloheximide blocked both root and shoot acclimation, indicating that both acclimation mechanisms are dependent on protein synthesis.

Abscisic Acid↗

PubMed1999

Arabidopsis ent-kaurene oxidase catalyzes three steps of gibberellin biosynthesis.

The Arabidopsis GA3 cDNA was expressed in yeast (Saccharomyces cerevisiae) and the ability of the transformed yeast cells to metabolize ent-kaurene was tested. We show by full-scan gas chromatography-mass spectrometry that the transformed cells produce ent-kaurenoic acid, and demonstrate that the single enzyme GA3 (ent-kaurene oxidase) catalyzes the three steps of gibberellin biosynthesis from ent-kaurene to ent-kaurenoic acid.

Arabidopsis↗

PubMed1999

The FLF MADS box gene: a repressor of flowering in Arabidopsis regulated by vernalization and methylation.

A MADS box gene, FLF (for FLOWERING LOCUS F ), isolated from a late-flowering, T-DNA-tagged Arabidopsis mutant, is a semidominant gene encoding a repressor of flowering. The FLF gene appears to integrate the vernalization-dependent and autonomous flowering pathways because its expression is regulated by genes in both pathways. The level of FLF mRNA is downregulated by vernalization and by a decrease in genomic DNA methylation, which is consistent with our previous suggestion that vernalization acts to induce flowering through changes in gene activity that are mediated through a reduction in DNA methylation. The flf-1 mutant requires a greater than normal amount of an exogenous gibberellin (GA3) to decrease flowering time compared with the wild type or with vernalization-responsive late-flowering mutants, suggesting that the FLF gene product may block the promotion of flowering by GAs. FLF maps to a region on chromosome 5 near the FLOWERING LOCUS C gene, which is a semidominant repressor of flowering in late-flowering ecotypes of Arabidopsis.

Arabidopsis↗

PubMed1999

Surgery for the treatment of medically intractable infantile spasms: a cautionary case.

UNLABELLED: The most appropriate time to consider cortical resection to treat medically intractable infantile spasms has not been clearly defined. The risks that need to be reconciled to make this decision are: What is the risk of loss of developmental potential if surgery is delayed too long versus what is the risk of unnecessary surgery if it is done too soon. We propose that, in addition to evaluation of seizures, developmental assessment is a key factor in the surgical decision. The case report illustrates this concept. CASE REPORT: HC had onset of seizures at 9 days of age and developed infantile spasms due to mild right hemimegancephaly. At 19 months, she was having up to 50 seizures/day and was evaluated and approved for right hemispherectomy but surgery was delayed. Despite the seizures, her development had been much better than most patients with hemimegencephaly and infantile spasms. At 25 months her seizure control was much improved but she had several seizures/week. EcoG at the time of surgery did not demonstrate the usual abnormalities so no resection was performed. She has had only 5 seizures in the 2(1/2) year since. CONCLUSIONS: (a) Hemimegalencephaly is not always associated with severe mental retardation; (b) normal or near-normal development may, in some cases, indicate the possibility of medical control of seizures as the child grows; (c) a localized developmental brain abnormality in a child with intractable seizures should not necessarily lead to cortical resection; and (d) when a child meets developmental milestones, it may be appropriate to delay surgical intervention.

Age Factors↗

PubMed1999

Postoperative seizure control and antiepileptic drug use in pediatric epilepsy surgery patients: the UCLA experience, 1986-1997.

PURPOSE: Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long-term seizure control. METHODS: This study determined pre- and postsurgery seizure frequency and antiepileptic drug (AED) use (6 months to 10 years) in children with symptomatic seizures from unilateral cortical dysplasia (CD; n = 64) and non-CD etiologies (i.e., ischemia, infection; n = 71), and compared them with older temporal lobe epilepsy (TLE; n = 31) patients with complex partial seizures. RESULTS: Compared with presurgery, postsurgery seizure frequencies were decreased for CD, non-CD, and TLE patients (p < 0.002), and there were no differences between the three groups from 6 to 24 months after surgery (p > 0.12). At 5 years after surgery, seizure frequencies were greater in CD compared with TLE cases (p = 0.009). Compared with presurgery, the number of AEDs declined after surgery in all three groups (p < 0.002), and positively correlated with seizure frequencies (p = 0.0001). CONCLUSIONS: This study indicates that seizure relief and AED use after resective surgery for symptomatic CD and non-CD etiologies was comparable with complex partial TLE cases up to 2 years after surgery. Furthermore, at 5 years after surgery, CD patients had outcomes better than those before surgery, but worse than TLE cases. In young children, these findings support the concept that early removal of symptomatic pathologic substrates is associated with seizure control and reduced AED use, similar to that noted in older TLE cases up to 2 years after surgery. Seizure control may reduce the risk of developing the seizure-related encephalopathy associated with severe symptomatic early-onset childhood epilepsy.

Age Factors↗

PubMed1999

Electrophysiological and morphological analyses of cortical neurons obtained from children with catastrophic epilepsy: dopamine receptor modulation of glutamatergic responses.

The present study examined the electrophysiological effects produced by activation of specific dopamine (DA) receptors and the distribution of DA receptor subtypes and glutamate receptor subunits [N-methyl-D-aspartate (NMDAR1) and GluR1] in cortical tissue samples obtained from children (ages 3 months to 16 years) undergoing epilepsy surgery. DA receptor activation produced differential effects depending on the receptor subtype that was activated. D1 receptor family agonists generally enhanced cortical excitability and favored the emergence of epileptogenic activity. In contrast, D2 receptor family agonists had more variable effects on cortical excitability and the expression of epileptiform discharges. Activation of D1 or D2 receptors decreased the amplitude of non-NMDA-mediated excitatory postsynaptic potentials. In contrast, DA and D1 agonists increased the amplitude of NMDA-mediated potentials. Immunohistochemical analysis showed that the DA receptor subtypes and glutamate receptor subunits examined were present in all cortical layers and areas throughout development. Whole-cell voltage clamp recordings of pyramidal neurons visualized with differential interference contrast optics and infrared videomicroscopy indicated that these neurons displayed a persistent Na(+) current, followed by an outward current. DA reduced the outward current but had little effect on the persistent Na(+) current. These results suggest a dual role for DA's actions in the human cerebral cortex. Activation of D2 receptors or antagonism of D1 receptors may help control seizures in children.

Adolescent↗

PubMed1999

MR artifact mimicking a temporal lobe lesion in an epilepsy patient.

A ten-year-old healthy child presented with a right upper extremity focal seizure which secondarily generalized. Magnetic resonance imaging (MR) revealed a 1-cm area of abnormal signal intensity in the left posterior temporal lobe at the gray-white junction. This did not appear on all imaging sequences, raising the suspicion of an artifact. Repeat MR revealed no intracranial or extracranial pathology. This case illustrates MR 'wrap around' artifact that mimicked a temporal lobe abnormality in an epilepsy patient. The physics of MR are reviewed as they pertain to this artifact.

Artifacts↗

PubMed1999

Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy.

OBJECTIVE: Sodium-coupled transporters remove extracellular neurotransmitters and alterations in their function could enhance or suppress synaptic transmission and seizures. This study determined hippocampal gamma-aminobutyric acid (GABA) and glutamate transporter immunoreactivity (IR) in temporal lobe epilepsy (TLE) patients. METHODS: Hippocampal sclerosis (HS) patients (n = 25) and non-HS cases (mass lesion and cryptogenic; n = 20) were compared with nonseizure autopsies (n = 8). Hippocampal sections were studied for neuron densities along with IR for glutamate decarboxylase (GAD; presynaptic GABA terminals), GABA transporter-1 (GAT-1; presynaptic GABA transporter), GAT-3 (astrocytic GABA transporter), excitatory amino acid transporter 3 (EAAT3; postsynaptic glutamate transporter), and EAAT2-1 (glial glutamate transporters). RESULTS: Compared with autopsies, non-HS cases with similar neuron counts showed: 1) increased GAD IR gray values (GV) in the fascia dentata outer molecular layer (OML), hilus, and stratum radiatum; 2) increased GAT-1 OML GVs; 3) increased astrocytic GAT-3 GVs in the hilus and Ammon's horn; and 4) no IR differences for EAAT3-1. HS patients with decreased neuron densities demonstrated: 1) increased OML and inner molecular layer GAD puncta; 2) decreased GAT-1 puncta relative to GAD in the stratum granulosum and pyramidale; 3) increased GAT-1 OML GVs; 4) decreased GAT-3 GVs; 5) increased EAAT3 IR on remaining granule cells and pyramids; 6) decreased glial EAAT2 GVs in the hilus and CA1 stratum radiatum associated with neuron loss; and 7) increased glial EAAT1 GVs in CA2/3 stratum radiatum. CONCLUSIONS: Hippocampal GABA and glutamate transporter IR differ in TLE patients compared with autopsies. These data support the hypothesis that excitatory and inhibitory neurotransmission and seizure susceptibility could be altered by neuronal and glial transporters in TLE patients.

ATP-Binding Cassette Transporters↗

PubMed1998

Cloning of the Arabidopsis ent-kaurene oxidase gene GA3.

The ga3 mutant of Arabidopsis is a gibberellin-responsive dwarf. We present data showing that the ga3-1 mutant is deficient in ent-kaurene oxidase activity, the first cytochrome P450-mediated step in the gibberellin biosynthetic pathway. By using a combination of conventional map-based cloning and random sequencing we identified a putative cytochrome P450 gene mapping to the same location as GA3. Relative to the progenitor line, two ga3 mutant alleles contained single base changes generating in-frame stop codons in the predicted amino acid sequence of the P450. A genomic clone spanning the P450 locus complemented the ga3-2 mutant. The deduced GA3 protein defines an additional class of cytochrome P450 enzymes. The GA3 gene was expressed in all tissues examined, RNA abundance being highest in inflorescence tissue.

Amino Acid Sequence↗

PubMed1998

DNA methylation and the promotion of flowering by vernalization.

We have tested the hypothesis that the promotion of flowering by prolonged exposure to low temperatures (vernalization) is mediated by DNA demethylation [Burn, J. E., Bagnall, D. J., Metzger, J. M., Dennis, E. S. & Peacock, W. J. (1993) Proc. Natl. Acad. Sci. USA 90, 287-291]. Arabidopsis plants that have reduced levels of DNA methylation because of the presence of a methyltransferase (METI) antisense gene flowered earlier than untransformed control plants, without the need for a cold treatment. Decreased DNA methylation mutants (ddm1) also flowered earlier than the wild-type progenitor under conditions where they respond to vernalization. We conclude that demethylation of DNA is sufficient to cause early flowering, and we have found that the promotion of flowering is directly proportional to the decrease in methylation in METI antisense lines. The early-flowering phenotype was inherited in sexual progeny, even when the antisense transgene had been lost by segregation. Methyltransferase antisense plants with low DNA methylation levels responded to a low-temperature treatment by flowering even earlier than their untreated siblings indicating that the promotion of flowering by cold and by demethylation was additive when neither treatment saturated the early-flowering response. As in untransformed control plants, the cold-induced early-flowering signal was reset in progeny of METI antisense plants. These observations suggest that the demethylation brought about by a METI antisense can account for some properties of vernalization, but not for the need for revernalization in each generation.

Arabidopsis↗

PubMed1998

Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients.

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.

Adult↗

PubMed1998

Eucalyptus has a functional equivalent of the Arabidopsis floral meristem identity gene LEAFY.

Two genes cloned from Eucalyptus globulus, Eucalyptus LeaFy (ELF1 and ELF2), have sequence homology to the floral meristem identity genes LEAFY from Arabidopsis and FLORICAULA from Antirrhinum. ELF1 is expressed in the developing eucalypt floral organs in a pattern similar to LEAFY while ELF2 appears to be a pseudo gene. ELF1 is expressed strongly in the early floral primordium and then successively in the primordia of sepals, petals, stamens and carpels. It is also expressed in the leaf primordia and young leaves and adult and juvenile trees. The ELF1 promoter coupled to a GUS reporter gene directs expression in transgenic Arabidopsis in a temporal and tissue-specific pattern similar to an equivalent Arabidopsis LEAFY promoter construct. Strong expression is seen in young flower buds and then later in sepals and petals. No expression was seen in rosette leaves or roots of flowering plants or in any non-flowering plants grown under long days. Furthermore, ectopic expression of the ELF1 gene in transgenic Arabidopsis causes the premature conversion of shoots into flowers, as does an equivalent 35S-LFY construct. These data suggest that ELF1 plays a similar role to LFY in flower development and that the basic mechanisms involved in flower initiation and development in Eucalyptus are similar to those in Arabidopsis.

Amino Acid Sequence↗

PubMed1998

Evidence for a role for AtMYB2 in the induction of the Arabidopsis alcohol dehydrogenase gene (ADH1) by low oxygen.

The transcription factor AtMYB2 binds to two sequence motifs in the promoter of the Arabidopsis ADH1 gene. The binding to the GT-motif (5'-TGGTTT-3') is essential for induction of ADH1 by low oxygen, while binding to the second motif, MBS-2, is not essential for induction. We show that AtMYB2 is induced by hypoxia with kinetics compatible with a role in the regulation of ADH1. Like ADH1, AtMYB2 has root-limited expression. When driven by a constitutive promoter, AtMYB2 is able to transactivate ADH1 expression in transient assays in both Arabidopsis and Nicotiana plumbaginifolia protoplasts, and in particle bombardment of Pisum sativum leaves. Mutation of the GT-motif abolished binding of AtMYB2 and caused loss of activity of the ADH1 promoter in both transient assays and transgenic Arabidopsis plants. These results are consistent with AtMYB2 being a key regulatory factor in the induction of the ADH1 promoter by low oxygen.

Alcohol Dehydrogenase↗