Regulation of the mitogen-activated protein kinase kinase (MEK)-1 by NAD(+)-dependent deacetylases.

Sirtuins are class III deacetylases that regulate many essential processes, including cellular stress, genome stability and metabolism. Although these NAD(+)-dependent deacetylases control adaptive cellular responses, identification of sirtuin-regulated signaling targets remain under-studied. Here, we demonstrate that acetylation of the mitogen-activated protein kinase kinase-1 (MEK1) stimulates its kinase activity, and that acetylated MEK1 is under the regulatory control of the sirtuin family members SIRT1 and SIRT2. Treatment of cells with sirtuin inhibitors, or siRNA knockdown of SIRT1 or SIRT2 proteins, increases MEK1 acetylation and subsequent phosphorylation of the extracellular signal-regulated kinase. Generation of an acetyl-specific MEK1 antibody demonstrates that endogenous acetylated MEK1 is extensively enriched in the nucleus following epidermal growth factor  stimulation. An acetyl-mimic of MEK1 increases inappropriate growth properties, suggesting that acetylation of MEK1 has oncogenic potential.

Inferior division third nerve paresis from an orbital dural arteriovenous malformation.

Isolated inferior division third nerve palsies are rare. The authors report a patient with an isolated, pupil-involving inferior division third cranial nerve palsy from an intraorbital dural arteriovenous malformation. Despite spontaneous thrombosis of the malformation, the third nerve palsy persisted. To the authors' knowledge, this is the first case report of an inferior division third nerve palsy caused by an orbital dural arteriovenous malformation.

Vertical and horizontal meridian sparing in occipital lobe homonymous hemianopias.

We report two patients with unique homonymous hemianopias from occipital lobe infarctions. One patient had vertical meridian sparing, and the other displayed horizontal meridian sparing. MRI correlation with the visual field defects confirmed that the vertical hemianopic meridian was represented along the border of the calcarine lips, and the horizontal meridian lies at the base of the calcarine banks deep within the calcarine fissure.

The central visual field in homonymous hemianopia. Evidence for unilateral foveal representation.

BACKGROUND: Controversy exists regarding the cortical representation of the foveal region in man. The most plausible explanation for foveal sparing in homonymous hemianopia is dual blood supply to the occipital pole. However, bilateral cortical representation has also been suggested. OBJECTIVE: To determine the representation of the foveal region in the primary human visual cortex. DESIGN: A case series correlating magnetic resonance imaging to the visual field defects of 6 patients with occipital lobe injuries. RESULTS: Four patients with foveal-sparing hemianopic defects demonstrated unilateral sparing of the posterior occipital cortex. In contrast, 2 patients with central homonymous defects showed isolated involvement of the posterior pole. One patient also demonstrated 5 degrees of field sparing along the horizontal meridian. CONCLUSIONS: On the basis of correlating the findings of magnetic resonance imaging and visual field defects in patients with occipital lobe injury, we conclude that the foveal region is unilaterally represented in the primary human visual cortex and that a major portion of the striate cortex is dedicated to the central 10 degrees of vision. The horizontal meridian of the visual field is represented deep within the calcarine banks at the fissure base.

Unilateral ptosis and contralateral eyelid retraction from a thalamic-midbrain infarction. Magnetic resonance imaging correlation.

We report a patient with a third nerve palsy and contralateral eyelid retraction from a thalamic-midbrain infarction. Magnetic resonance imaging confirms that this unusual clinical combination, previously termed "the plus-minus lid syndrome," results from a lesion in the region of the nucleus of the posterior commissure with extension to the third nerve fascicle.

SPECT in patients with cortical visual loss.

Single-photon emission computed tomography (SPECT) with 99mTc-hexamethylpropyleneamine oxime (HMPAO) was used to investigate changes in cerebral blood flow in seven patients with cortical visual impairment. Traumatic brain injury (TBI) was the cause of cortical damage in two patients, cerebral ischemia in two patients and carbon monoxide (CO) poisoning, status epilepticus and Alzheimer's Disease (AD) each in three separate patients. The SPECT scans of the seven patients were compared to T2-weighted magnetic resonance image (MRI) scans of the brain to determine the correlation between functional and anatomical findings. In six of the seven patients, the qualitative interpretation of the SPECT studies supported the clinical findings (i.e., the visual field defect) by revealing altered regional cerebral blood flow (rCBF) in the appropriate regions of the visual pathway. MR scans in all of the patients, on the other hand, were either normal or disclosed smaller lesions than those detected by SPECT. We conclude that SPECT may reveal altered rCBF in patients with cortical visual impairment of various etiologies, even when MRI studies are normal or nondiagnostic.

Pretectal eyelid retraction and lag.

We report 2 patients who had eyelid retraction and eyelid lag with minimal impairment of vertical gaze. In both patients, magnetic resonance imaging demonstrated a circumscribed unilateral lesion immediately rostral and dorsal to the red nucleus involving the lateral periaqueductal gray area. Our clinical and radiological findings support the existence of a premotor eyelid control center in the region of the nucleus of the posterior commissure.

Ocular tilt reaction resulting from vestibuloacoustic nerve surgery.

The ocular tilt reaction (OTR) is a triad of head-eye synkinesis composed of head tilt, conjugate ocular torsion in the direction of head tilt, and skew deviation. The OTR represents a normal compensatory response to lateral head tilts and is produced by activation of the utricle of the lowermost ear. A pathological OTR results when otolith activity is unopposed as the result of injury to the opposite utricle or its nerve. Vertical diplopia may be the only symptom of OTR in patients who have undergone surgery involving the vestibuloacoustic nerve. We report a series of patients with OTR after surgery for acoustic neuroma or Meniere's disease. In each patient, the manifesting symptom was vertical diplopia. Bedside neuro-ophthalmological testing readily excluded a brain stem cause for the double vision. We conclude that OTR after vestibuloacoustic surgery is a benign condition with spontaneous resolution of symptoms within several months.

Avoiding adverse effects of cycloplegics in infants and children.

Cycloplegics are very safe and useful medications. To avoid the unpleasant side effects of these medications, six precautions are considered. They are: 1. dosage, 2. cycloplegic selection, 3. toxic reaction, 4. biologic variations, 5. topical anesthesia, 6. environmental temperature and humidity.

Effects of streptovaricins and their degradation products on RNA-directed DNA polymerase of Rauscher leukemia virus.

The activities of streptovaricin complexes, streptovaricins, streptovals, and streptovarinic degradation products were elevated against RNA-directed DNA polymerases of Rauscher leukemia virus, DNA-dependent DNA polymerase of bacterial and mammalian cells, and DNA-dependent RNA polymerases of mammalian origin. The activities of streptovaricins were also listed for comparison purposes. The effects of streptovaricin complexes on viral DNA polymerases varied significantly from lot to lot, and streptovaricin complex lot 7 was the most active. All the streptovals and streptovaricin degradation products except varicinal A showed a marked improvement (twofold to tenfold) in activity against the viral enzyme over the parent streptovaricins. None of these compounds, however, displayed any significant effect on either the DNA polymerase of L1210 leukemia cells and Escherichia coli or the RNA polymerase of isolated nuclei of mouse liver. As a result of tests in these systems, some specific inhibitors of RNA-directed DNA polymerases of Rauscher leukemia virus were selected.

Nucleic acids. 16. Orally active derivatives of ara-cytidine.

Water-soluble derivatives of ara-cytidine (cytarabine, Cytosar) were prepared and tested for antitumor, immunosuppressive, and antiarthritic activities in animals after oral administration. The compounds tested included the 5'-palmitate, 5'-benzoate, and 5'-adamantoate esters of ara-cytidine, made water soluble by use of their hydrochloride salts of peptidyl derivatives, and two basic 5' esters (5'-nicotinoate and 5'-quinuclidinate) as their hydrochloride salts. Five of the compounds had antitumor activity superior to that found with ara-cytidine itself after oral administration in the L1210 leukemic mouse assay. One of these, 5'-adamantoyl-ara-cytidine hydrochloride, had antitumor activity after oral administration approaching that achieved with parenterally administered ara-cytidine.