Plant response to drought and hyperosmosis is mediated by the phytohormone abscisic acid (ABA), a sesquiterpene compound widely distributed in various embryophyte groups. Exogenous ABA as well as ...hyperosmosis activates the sucrose nonfermenting 1 (SNF1)-related protein kinase2 (SnRK2), which plays a central role in cellular responses against drought and dehydration, although the details of the activation mechanism are not understood. Analysis of a mutant of the mossPhyscomitrella patenswith reduced ABA sensitivity and reduced hyperosmosis tolerance revealed that a protein kinase designated “ARK” (for “ABA and abiotic stress-responsive Raf-like kinase”) plays an essential role in the activation of SnRK2. ARK encoded by a single gene inP. patensbelongs to the family of group B3 Raf-like MAP kinase kinase kinases (B3-MAPKKKs) mediating ethylene, disease resistance, and salt and sugar responses in angiosperms. Our findings indicate that ARK, as a novel regulatory component integrating ABA and hyperosmosis signals, represents the ancestral B3-MAPKKKs, which multiplied, diversified, and came to have specific functions in angiosperms.
Abstract We report here on 8 infants who showed paroxysmal downwards gaze (PDG). The time of initial appearance of PDG ranged from one month to five months (mean: 2.7 months) of corrected age. Seven ...out of eight patients showed interictal spikes in EEG, so they were started on prophylactic therapy with antiepileptic drugs. In five of the eight patients, PDG ceased, either spontaneously or with antiepileptic drug treatment, by four to eight months of corrected age. Six out of eight patients showed localized spikes and peculiar abnormal fast activity (AFA) in the occipital area and five of these patients later developed West syndrome. These AFA were observed on EEGs recorded at the time of initial PDG appearance, before hypsarrhythmia was observed and before tonic spasms appeared. We were able to exclude the possibility that PDG was a subtle epileptic seizure by confirming the temporal discordance between individual episodes of PDG and AFA with video-EEG monitoring. Yet topographic data showed that AFA in these patients was characteristically located in the occipital area, with a distribution similar to that of the fast activity which accompanied the tonic spasms that later developed in these patients. As a risk factor for developing WS, we propose the clinical symptom of PDG with characteristic occipital AFA visible in the EEG, both of which represent damage to the occipital region including the optic radiation.
Abscisic acid (ABA) is a plant hormone important for environmental stress responses. We identified the Raf-like protein kinase ARK as an upstream regulator of subclass III sucrose ...non-fermenting1-related kinase2, known as a key activator of ABA signaling in Physcomitrella patens. Phosphopeptide mapping revealed that ARK is phosphorylated at a specific Ser residue in the activation loop of the kinase domain. Substitution of the Ser residue to Ala caused a decrease in ABA-induced gene expression while that to Asp caused an enhancement of the gene expression. From these results, we conclude that phosphorylation of ARK is important for its kinase activity and a response to ABA.
Abscisic acid (ABA) controls plants’ tolerance to environmental stress such as freezing and desiccation. Wepreviously reported that AR7, the ABA-insensitive mutant of Physcomitrella patens has a ...defect in the ARKgene encoding the group B3 MAP kinase kinase kinase, with a single amino acid change from serine tophenylalanine in the non-kinase domain having a putative regulatory function. By ultraviolet mutagenesis,we obtained over one hundred ABA-insensitive mutants, from which two ark nonsense mutants wereidentified. These mutants showed inhibited protonemal growth with elongated gametophore in the absence ofABA, in contrast to AR7 showing protonemal growth similar to wild type. These results indicate that ARK isinvolved in regulation of plant growth in addition to stress responses.
We have observed paroxysmal automatic movements including drum-beating and pedaling motions in three full-term neonates following intravenous bolus injections (0.1-0.3 mg/kg/dose) or drip infusions ...(0.2 mg/kg/h) of midazolam used for sedation. In one patient, abnormal movements were also induced by a bolus injection of midazolam during the EEG recording, and no change was revealed in the EEG during the episode. In another patient, abnormal movements were further worsened by an injection of diazepam. Interictal EEGs of all patients were normal. The clinical manifestations of these paroxysmal automatic movements and the mode of their appearance were quite similar in all patients. It is quite likely that abnormal movements in the patient without ictal EEG change do not have epileptic origin but brainstem release phenomenon induced by midazolam. Because the abnormal movements in the other two cases had similar clinical manifestations and mode of appearance, we suspected that these movements were also non-epileptic though ictal EEGs were not recorded in theses cases. When we encounter paroxysmal automatic movements mimicking neonatal seizures following intravenous midazolam administration, ictal EEG recordings are recommended. If there are no ictal changes, we should avoid treatment with anticonvulsant drugs for these movements. Since midazolam is frequently used in neonates for sedation during various examinations, future investigations on the selection of appropriate drugs and dosage for sedation in neonates, including the usage of midazolam, are necessary.
We observed characteristic involuntary movements in premature babies during early infancy. These movements consisted of asymmetrical irregular banging of the extremities, similar to chorea, ballisms, ...or jitteriness. We investigated the clinical characteristics and neuroimaging findings of the patients with these peculiar involuntary movements to clarify their pathophysiological mechanisms and to find a treatment. In our sequential follow-up study on 90 premature infants with various pre-and perinatal brain insults, we found various types of cerebellar injuries in 28 patients. In 19 of these, the prominent injuries were observed in the inferior cerebellar hemispheres. These cerebellar injuries were often observed in patients born before the gestational age of 27 weeks. Fourteen of the 28 patients with cerebellar injuries displayed the above-mentioned characteristic involuntary movements. Twelve of these 14 patients with both cerebellar injury and involuntary movements were born before the gestational age of 27 weeks. On the contrary, 10 patients with cerebellar injury born after the gestational age of 27 weeks did not display these peculiar involuntary movements. It is noteworthy that cerebral injuries were not associated with the occurrence of these involuntary movements. Two patients with asymmetrical cerebellar deformity caused by compression due to a cystic lesion did not show these involuntary movements. The movements appeared around the corrected age of 3 months, and they disturbed the patients' acquisition of sitting ability. Nine patients with these involuntary movements developed severe athetotic cerebral palsy. These movements showed drug resistance, however, benzodiazepines had a partial effect in some patients. Recently, cerebellar injury in premature infants has received a lot of attention. We believe that the peculiar involuntary movements we observed in the present patient group may be caused by a particular type of cerebellar damage specific to premature infants born before 27 weeks of gestational age.
Vitamin B6 (VB6) is used frequently as one of the first-choice drug for the treatment of West syndrome (WS) in Japan. We report 2 cases of symptomatic WS who had a good response to readministration ...of VB6. Case 1 was a 3-year-old girl diagnosed as having severe hydroencephalus. She developed WS at the age of 9 months. She was treated with ACTH, but relapsed when she was 1 year old. Despite treatment with various conventional drugs and second ACTH therapy, her seizures were not suppressed. We reviewed past treatment records in another hospital, and found that VB, treatment was stopped because her EEG did not improve within a week. We then retried VB6 therapy when she was 3 years and 6 months old, and as a result she became seizure-free and hypsarrhythmia disappeared on EEG within a month. Case 2 was a boy with severe cerebral palsy who was diagnosed as having WS at the age of 9 months. His MRI revealed bilateral subdural hematoma. Treatment was started with VB6, and he became seizure-free within several days. But 7 days after starting VB6, treatment was stopped because of the side effects. VPA was started instead, but his EEG showed gradual worsening. Then, we added a smaller dose of VB6 to VPA. His EEG improved dramatically, and his seizures have been controlled without any side effects. The present cases indicate the possible clinical usefulness of successful VB6 retrials even in older patients with severe organic lesions, by means of combined therapy with other drug, and alternative design of the dosing. However, we suspect there might be many cases in which the efficacy of VB6 therapy has not been properly assessed due to the short observation period and/or side effects.
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