Anti-NMDA receptor encephalitis presenting with focal non-convulsive status epilepticus in a child.

A previously healthy 9-year-old girl presented to an emergency department (ED) with headache, dizziness, blurry vision, and abnormal visual perceptions. She was diagnosed with migraine, treated symptomatically, and discharged. Over the course of days, she became progressively somnolent, and returned to the ED, where she was found to have a right inferior quadrantanopsia and sixth nerve palsy. Magnetic resonance imaging (MRI) of the brain showed gyral swelling of the left parieto-occipital lobe. Continuous electroencephalogram (EEG) monitoring revealed focal non-convulsive status epilepticus (NCSE) in the left occipital region. Cerebrospinal fluid (CSF) was positive for antibodies directed against the N-methyl-d-aspartate receptor (NMDAR). This case is the first report of anti-NMDAR encephalitis presenting with focal non-convulsive status epilepticus (NCSE).

The structure and regulation of the oxytocin receptor.

The oxytocin receptor (OTR) is part of an ancient hormone system expressed in diverse phyla in relation to acute reproductive smooth muscle responses, such as egg-laying, birth, or milk letdown. The regulation of the OTR gene, while correlating with steroid levels in vivo, remains elusive. There appear to be both inhibitory and stimulatory influences acting upon a constitutive pattern of basal expression. We have found no evidence, however, for an effect of the sex steroids either directly on gene transcription, or on the receptor itself at the protein level. In the prostatic carcinoma cell line Du145, we have shown that up-regulation of the OTR gene transcription can be effected by cAMP. In an attempt to characterize the expression of the OTR protein in vivo, we have shown, using ligand-blotting, that the OTR can be expressed at different sizes in transfected cells and in myometrium. Also, in the myometrium at term, immunohistochemistry suggests that there is both an increase in OTR protein per cell, as well as in the number of smooth muscle cells expressing OTR, emphasizing that perinatal changes are the results of both individual gene activation events and gross cellular differentiation. The OTR is a valuable model system reflecting molecular changes in the perinatal period. When we understand how this important molecule is regulated, we will also be a long way towards understanding the mechanisms controlling myometrial contractility at birth. Experimental Physiology (2001) 86.2, 289-296.

Novel splicing variants of the human thyrotropin receptor encode truncated polypeptides without a membrane-spanning domain.

The thyrotropin receptor is of fundamental importance to normal thyroid function and is considered to be the predominant antigen affected by the autoantibodies of Graves' autoimmune hyperthyroidism. The identification of the epitopes on the receptor to which the autoantibodies bind or the mechanism by which the autoantibodies arise remain to be established. In this report we have analysed in detail thein vivo transcription of the human TSH receptor gene (hTSH-R), demonstrating the presence of numerous novel TSH receptor transcripts. Northern blot analysis of mRNA from human thyroid tissue using a radiolabelled cDNA probe specific for the extracellular domain of the hTSH-R revealed the presence of small polyadenylated mRNAs, in addition to the full-length hTSH-R mRNA. A PCR strategy devised to clone transcripts with 3' polyadenylation and 5' hTSH-R specific sequences was used to clone five different hTSH-R transcripts (hTSH-R. ST1 to ST5; 250bp-1.7 kb) from human thyroid tissue. Sequence analysis demonstrated that the small transcripts arose by alternative splicing of the hTSH-R mRNA. The transcripts were associated with polysomes and were demonstrated in human thyroid tissue from patients suffering from Graves' disease, sporadic goiter as well as in healthy lobes of thyroid tissue.In situ hybridization demonstrated that two of the alternative transcripts adopted a tissue distribution pattern identical to that of the full-length hTSH-R transcript. The two major truncated transcripts ST4 and ST5 contained unique sequences at the 3' end of the mRNAs and thus potentially represent the molecular origin of soluble TSH receptor variants which have been postulated on numerous occasions.