Absence of tonic electromyographic activity during sleep in normal and spastic nonmimetic skeletal muscles in man

An electromyographic study of nonmimetic skeletal muscles was carried out in 8 normal adults and 4 patients with spastic hemiparesis during all stages of sleep for a total of 21 nights. All normal subjects showed absence of tonic electromyographic activity in all nonmimetic skeletal muscles in all stages of sleep. Also, during quiet, relaxed wakefulness, tonic muscle discharges disappeared in the normal subjects. Three patients with upper motor neuron spasticity demonstrated results during sleep similar to those obtained in the normal subjects. In the fourth patient, tonic muscle discharges persisted into stage 2 non-REM sleep, disappeared within 30 to 240 seconds following the onset of stage 2 sleep, and were absent during stages 3 and 4 sleep and REM sleep.     

Developmental characteristics of histamine methyltransferase and phenylethanolamine-N-methyl-transferase of rat brain

The specific activity of histamine methyltransferase of rat brain increases rapidly from the 16th until the 25th day of gestation (7 days after birth). The specific activity of phenylethanolamine-N-methyl-transferase shows a rapid increase during the 1st and the 2nd week after birth, the adult values being obtained by the end of the 2nd week.     

Subconjunctival mitomycin C for the treatment of ocular cicatricial pemphigoid

PURPOSE: The authors performed a prospective evaluation of the efficacy of treating ocular cicatricial pemphigoid (OCP) with subconjunctival mitomycin C. DESIGN: Unmasked, prospective, internally controlled case series. METHODS: Patients were eligible for treatment with subconjunctival mitomycin C under three criteria: (1) significant complications of systemic immunosuppressant therapy; (2) markedly asymmetric conjunctival disease; and (3) end-stage OCP. All patients received monocular subconjunctival injections of 0.25 ml of 0.2 mg/ml mitomycin C to both the superior and inferior bulbar conjunctivae in the eye with the more severe disease. RESULTS: Nine eyes of nine patients (mean age, 74 years) were treated with subconjunctival mitomycin C to the more-involved eye and were followed for a mean of 23.5 months (range, 12-40 months). Eight of nine patients showed quiescence of their OCP in the treated eye based on serial evaluation of conjunctival cicatrization and grading of conjunctival erythema. Five of the nine untreated eyes showed progression of the conjunctival disease. One patient required concomitant systemic immunosuppressive therapy after subconjunctival mitomycin C. Two patients underwent successful visual rehabilitative surgery in the mitomycin C-treated eye. CONCLUSION: The use of subconjunctival mitomycin C may be effective in preventing progression of conjunctival cicatrization and erythema in patients with OCP. No complications of mitomycin C treatment were noted. Long-term follow-up and further investigation into the efficacy of subconjunctival mitomycin C in the management of OCP is warranted.     

Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABAA receptors

A pharmacophore and an alignment rule have previously been reported for BzR agonist ligands. The design and synthesis of 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC, 24, IC50 = 8.1 nM) was based on this pharmacophore. When evaluated in vivo this ligand exhibited anticonvulsant/anxiolytic activity but was devoid of the muscle relaxant/ataxic effects of "classical" 1,4-benzodiazepines (i.e., diazepam). Significantly, 6-PBC 24 also reversed diazepam-induced muscle relaxation in mice. The 3-substituted analogues 40-46 and 48 of 6-PBC 24 and Zk 93423 27(IC50 = 1 nM) were synthesized and evaluated in vitro to determine what affect these modifications would have on the binding affinity at recombinant BzR subtypes. With the exception of the 3-amino ligands 40 and 41, all the beta-carbolines were found to exhibit high binding affinity at BzR sites. The 3-propyl ether derivative 45 was also evaluated in vivo and found to be devoid of any proconvulsant or anticonvulsant activity at doses up to 40 mg/kg. The 6-(1-naphthylmethyloxy) and 6-octyloxy analogues 25, 26, 28, and 29 of 6-PBC 24 were synthesized to further evaluate the proposed alignment of agonists vs inverse agonists in the pharmacophore of the BzR. In addition, ligands 26 and 29 were designed to probe the dimensions of lipophilic pocket L3 at the agonist site. The activity of 29 was evaluated in vivo; however, this analogue elicited no pharmacological effects at doses up to 80 mg/kg. These and other related beta-carbolines were also examined in five recombinant GABAA receptor subtypes. Ligands 52-61 all exhibited moderate to high affinity at GABAA receptors containing alpha1 subunits. These ligands will be useful in further defining the pharmacophore at alpha1 beta3 gamma2 receptors.     

THE FLUID MECHANICS of COOKIE DOUGH EXTRUDERS

A model of the fluid mechanics of two roll cookie dough extruders, such as used for wire cut and rout cookies, is presented. the model uses the lubrication approximation to obtain a first estimate for the predictive equations for extruder capacity, power consumption, total shear strain, and forces developed by the rolls. These equations are used to understand the importance of various design and operational parameters.     

Covariation of activity in visual and prefrontal cortex associated with subjective visual perception

Visual areas of the occipitotemporal pathway are thought to be essential for the conscious perception of objects, but the contribution of other cortical regions and the neural mechanisms leading to the awareness of a visual stimulus remain unclear. By using functional MRI in humans exposed to bistable viewing conditions, subjective visual perception was related to covariation of activity in multiple extrastriate ventral, parietal, and prefrontal cortical areas. The coordination of activity among these regions was not linked to external sensory or motor events; rather, it reflected internal changes in perception and varied in strength with the frequency of perceptual events, suggesting that functional interactions between visual and prefrontal cortex may contribute to conscious vision. Because similar cortical systems have been implicated in short-term memory and motor planning, the results also imply that related neural processes may underlie visual awareness and the organization of voluntary behavior contingent on sensory cues.     

Cryptic invasions of the crab Carcinus detected by molecular phylogeography

Coastal marine ecosystems world-wide are threatened by invasions of nonindigenous species. The ubiquity of marine sibling species identifiable only by genetic analysis suggests that many invasions are cryptic and therefore undetected, causing an underestimation of the actual number and impacts of invading species. We test this hypothesis with European crabs in the genus Carcinus that have invaded five regions globally. Partial 16S ribosomal RNA gene sequences confirm sibling species status of morphologically similar Atlantic C. maenas and Mediterranean C. aestuarii. Based on 16S rRNA haplotypes, crabs from California, New England and Tasmania were all C. maenas. However, we report the cryptic multiple invasion of both species in Japan and South Africa, where only C. aestuarii and C. maenas, respectively, were previously recognized.     

Role of the TRAF binding site and NF-kappaB activation in Epstein-Barr virus latent membrane protein 1-induced cell gene expression

In this study, we investigated the induction of cellular gene expression by the Epstein-Barr Virus (EBV) latent membrane protein 1 (LMP1). Previously, LMP1 was shown to induce the expression of ICAM-1, LFA-3, CD40, and EBI3 in EBV-negative Burkitt lymphoma (BL) cells and of the epidermal growth factor receptor (EGF-R) in epithelial cells. We now show that LMP1 expression also increased Fas and tumor necrosis factor receptor-associated factor 1 (TRAF1) in BL cells. LMP1 mediates NF-kappaB activation via two independent domains located in its C-terminal cytoplasmic tail, a TRAF-interacting site that associates with TRAF1, -2, -3, and -5 through a PXQXT/S core motif and a TRADD-interacting site. In EBV-transformed B cells or transiently transfected BL cells, significant amounts of TRAF1, -2, -3, and -5 are associated with LMP1. In epithelial cells, very little TRAF1 is expressed, and only TRAF2, -3, and -5, are significantly complexed with LMP1. The importance of TRAF binding to the PXQXT/S motif in LMP1-mediated gene induction was studied by using an LMP1 mutant that contains alanine point mutations in this motif and fails to associate with TRAFs. This mutant, LMP1(P204A/Q206A), induced 60% of wild-type LMP1 NF-kappaB activation and had approximately 60% of wild-type LMP1 effect on Fas, ICAM-1, CD40, and LFA-3 induction. In contrast, LMP1(P204A/Q206A) was substantially more impaired in TRAF1, EBI3, and EGF-R induction. Thus, TRAF binding to the PXQXT/S motif has a nonessential role in up-regulating Fas, ICAM-1, CD40, and LFA-3 expression and a critical role in up-regulating TRAF1, EBI3, and EGF-R expression. Further, D1 LMP1, an LMP1 mutant that does not aggregate failed to induce TRAF1, EBI3, Fas, ICAM-1, CD40, and LFA-3 expression confirming the essential role for aggregation in LMP1 signaling. Overexpression of a dominant form of IkappaBalpha blocked LMP1-mediated TRAF1, EBI3, Fas, ICAM-1, CD40, and LFA-3 up-regulation, indicating that NF-kappaB is an important component of LMP1-mediated gene induction from both the TRAF- and TRADD-interacting sites.