Lidocaine-induced CNS toxicity--a case report

One hundred and twenty-six cases of cerebellopontine angle tumors with various histologies are presented. Results of 75 operated vestibular neurinomas, 22 meningiomas, and 16 tumors with other histologies are discussed. The method of irradiation and non-radical surgery may be an alternative for treatment.     

Effects of frusemide on the urinary excretion of dopamine and 5-hydroxytryptamine in normal man

The effects of frusemide on the urinary excretion of dopamine and 5-hydroxytryptamine (5-HT) were investigated in eight healthy male subjects in a randomized, placebo-controlled, cross-over study. Frusemide produced the expected rise in urinary dopamine excretion but it did not affect 5-HT excretion when compared with placebo. The lack of an effect on 5-HT excretion in man contrasts with studies in the rat which have reported a marked increase in 5-HT excretion after administration of this loop diuretic.     

Prenatal diagnosis of Apert syndrome

Apert syndrome (AS) is clinically characterized by typical facial features and symmetrical syndactyly of the digits. AS is inherited as an autosomal dominant trait. Recently, a fibroblast growth factor receptors 2 (FGFR2) mutation, either C934G or C937G, was identified in exon IIIa. Our report documents an affected mother and son in whom one of the two mutations in AS had occurred sporadically in the mother. The diagnosed of AS was based on associated abnormal physical features and on molecular genetic analysis. A C-to-G transversion at position 937 of the cDNA resulting in a proline-to-arginine substitution at codon 259 was found in the mother. In her second pregnancy, prenatal diagnosis by both restriction analysis and direct sequencing was undertaken and this showed that the female fetus had not inherited the mutation.     

Direction of temperature control in the thermal biofeedback treatment of vascular headache

In order to test for the specific therapeutic effects of thermal biofeedback (TBF) for hand warming on vascular headache (HA), 70 patients with chronic vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling, TBF for stabilization of hand temperature, or biofeedback to suppress alpha in the EEG. Patients in each condition initially had high levels of expectation of therapeutic benefit and found the treatment rationales highly credible. Participants in each condition received 12 treatment sessions on a twice-per-week basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and 4 weeks after treatment, HA Index was significantly (p = .003) reduced as was HA medication consumption. There were no differential reductions in HA Index or Medication Index among the four conditions. Global self-reports of improvement gathered at the end of the post-treatment monitoring period also did not differ among the four conditions. We were unable to demonstrate a specific effect of TBF for hand warming on vascular HA activity.     

Seasonal abundance and parity of stock-associated Culicoides species (Diptera: Ceratopogonidae) in different climatic regions in southern Africa in relation to their viral vector potential

We identified a Xenopus gene closely related to mammalian bone morphogenetic protein (BMP)-7 (also termed osteogenic protein-1 or OP-1). It resembles the mammalian gene in primary structure and expression pattern much more closely than does a previously described Xenopus homologue, originally termed XBMP-7 [Nishimatsu, Suzuki, Shoda, Murakami and Ueno (1992) Biochem. Biophys. Res. Commun. 186, 1487-1495]. The novel gene has therefore been designated XBMP-7 and the gene described earlier has been renamed XBMP-7R (M. Moos and N. Ueno, unpublished work). It has a broad distribution, primarily in the anterior and posterior ventral regions during gastrulation, subsequently becoming prominent at different stages in a wide variety of structures (eyes, neural structures, heart, pronephros, posterior ventral region and other structures), paralleling the distribution of XBMP-4 closely. However, its expression begins later than that of XBMP-4 during gastrulation. Lithium treatment of embryos concentrates the XBMP-7 expression in the expanded eye and heart structures. Ventral overexpression of XBMP-7 produces large protrusions that ultimately develop colouration characteristic of haemoglobin, which is confirmed by markedly expanded expression of alpha-globin. Dorsal overexpression suppresses dorsal anterior structures. Molecular analysis of animal caps overexpressing XBMP-7 reveals induction of markers associated with ventral and haematopoietic tissue, which is consistent with whole-embryo overexpression results. Globin induction by XBMP-7 can be blocked by a truncated BMP receptor previously shown to interrupt BMP-4 signalling, indicating XBMP-7 also interacts with this receptor. Our data support the concept that XBMP-7 may play a variety of roles during embryogenesis, and suggest a possible role in haematogenesis.     

Functional complementation of UL3.5-negative pseudorabies virus by the bovine herpesvirus 1 UL3.5 homolog

The UL3.5 gene is positionally conserved but highly variable in size and sequence in different members of the Alphaherpesvirinae and is absent from herpes simplex virus genomes. We have shown previously that the pseudorabies virus (PrV) UL3.5 gene encodes a nonstructural protein which is required for secondary envelopment of intracytoplasmic virus particles in the trans-Golgi region. In the absence of UL3.5 protein, naked nucleocapsids accumulate in the cytoplasm, release of infectious virions is drastically reduced, and plaque formation in cell culture is inhibited (W. Fuchs, B. G. Klupp, H. Granzow, H.-J. Rziha, and T. C. Mettenleiter, J. Virol. 70:3517-3527, 1996). To assay functional complementation by a heterologous herpesviral UL3.5 protein, the UL3.5 gene of bovine herpesvirus 1 (BHV-1) was inserted at two different sites within the genome of UL3.5-negative PrV. In cells infected with the PrV recombinants the BHV-1 UL3.5 gene product was identified as a 17-kDa protein which was identical in size to the UL3.5 protein detected in BHV-1-infected cells. Expression of BHV-1 UL3.5 compensated for the lack of PrV UL3.5, resulting in a ca. 1,000-fold increase in virus titer and restoration of plaque formation in cell culture. Also, the intracellular block in viral egress was resolved by the BHV-1 UL3.5 gene. We conclude that the UL3.5 proteins of PrV and BHV-1 are functionally related and are involved in a common step in the egress of alphaherpesviruses.     

Disruption of fibronectin binding to the alpha 5 beta 1 integrin stimulates the expression of cyclin-dependent kinases and DNA synthesis through activation of extracellular signal-regulated kinase

The alpha 5 alpha 1 integrin, a fibronectin receptor, has been implicated in the control of cell growth and the regulation of gene expression. We report that disruption of ligation between alpha 5 alpha 1 and fibronectin by integrin alpha 5 subunit or fibronectin monoclonal antibodies stimulated DNA synthesis in growth-arrested FET human colon carcinoma cells. This stimulation only occurred when monoclonal antibody was added in the early G1 phase of the cell cycle after release from quiescence by fresh medium. Stimulation of DNA synthesis by alpha 5 or fibronectin antibody was concentration- and time-dependent. FET cells expressed alpha 4 beta 1 integrin (another fibronectin receptor); however, addition of anti-human integrin alpha 4 monoclonal antibody had no effect on DNA synthesis. Treatment with alpha 5 monoclonal antibody led to a marked increase in the expression of CDK4 in G1 phase of the cell cycle and consequently increased the phosphorylation of retinoblastoma protein. alpha 5 monoclonal antibody treatment increased both cyclin A- and cyclin E-associated kinase activity which was accompanied by increased protein levels of CDK2 and cyclin A. Western blotting of immunoprecipitates demonstrated increased CDK2-cyclin E and CDK2-cyclin A complexes in cells treated with alpha 5 monoclonal antibody. Furthermore, disruption of alpha 5 alpha 1/fibronectin ligation activated mitogen-activated protein kinase p44 and p42 (extracellular signal-regulated kinase 1 and 2). Pretreatment of the cells with a specific inhibitor of MEK-1, PD98059, blocked the alpha 5 monoclonal antibody-induced mitogen-activated protein kinase activity. In addition PD98059 prevented alpha 5 monoclonal antibody-induced DNA synthesis. Since alpha 5 alpha 1 ligation to fibronectin is associated with decreased growth parameters, our results indicate that ligation of alpha 5 alpha 1 integrin to fibronectin results in suppressed mitogen-activated protein kinase activity which in turn inhibits cyclin-dependent kinase activity in growth-arrested cells.     

Types of purinoceptors and phospholipase A2 involved in the activation of the platelet-activating factor-dependent transacetylase activity and arachidonate release by ATP in endothelial cells

Acyl analogs of PAF are the major products synthesized during agonist stimulation of endothelial cells. We have previously shown that PAF: 1-acyl-2-lyso-sn-glycero-3-phosphocholine transacetylase in calf pulmonary artery endothelial cells is activated by ATP through protein phosphorylation, and the increase in transacetylase activity by ATP contributes to the biosynthesis of acyl analogs of PAF (J. Biol. Chem. 272, 17431-17437, 1997). To understand the mechanisms(s) by which ATP stimulates acyl analogs of PAF production, we have identified the subtypes of the purinergic receptor that are linked to the activation of two enzymes involved in the generation of acyl analogs of PAF, namely, transacetylase and phospholipase A2. Experiments with transient transfection of the cells with antisense and sense thio-oligonucleotide to cytosolic phospholipase A2 (cPLA2) were also performed to evaluate whether downstream activation of cPLA2 is involved in ATP-receptor mediated induction of arachidonate release and synthesis of radylacetyl-GPC. We found that the P2u/P2Y2 receptor, which recognizes a pyrimidine nucleotide, UTP, as well as purine nucleotides, shows a potency profile of UTP > ATP = ATP gamma S > 2-methylthio-ATP in mediating the activation of PAF: lysophospholipid transacetylase. On the other hand, ADP beta S and 2-methylthio-ATP have similar potencies as ATP but have lower potencies than UTP and ATP gamma S in stimulating the release of arachidonate. These results suggest that both P2u/P2Y2 and P2y/P2Y1 receptor subtypes promote arachidonate release. In addition, transient transfection of endothelial cells with cPLA2 antisense but not the sense thio-oligonucleotide inhibited the stimulation of arachidonate release and [3H]acetate incorporation into radyl[3H]acetyl-GPC. Thus, our data suggest that a receptor-mediated process is involved in the activation of transacetylase for the induced synthesis of acyl analogs of PAF in endothelial cells. Furthermore, it is likely that cPLA2 supplies the lysophospholipids as substrates for the transacetylation reaction.