Cheilo-candidosis in an adult

A rare case of candidal infection of the lips is presented. Predisposing factors appeared to be intra-oral candidal carriage, actinic lip damage and Sj?gren's syndrome. Systemic antifungal therapy with fluconazole resolved the initial infection and a subsequent recurrence.     

Production of a monoclonal antibody against the 128 kDa (CagA) protein of Helicobacter pylori

We report a case of herpes simplex encephalitis in which the patient was repeatedly examined by magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). The patient was a 36 year-old woman who had been transferred to our institution 6 days after the onset of symptoms with mild consciousness disturbance, nuchal rigidity, and high fever. Cerebrospinal fluid examination revealed an elevated mononuclear cell count with normal sugar concentration. Intravenous aciclovir was started 7 days after the onset of symptoms. The initial plain computed tomography (CT) scans did not reveal any abnormal findings, but contrast enhanced CT the next day showed a slight enhancement effect around the affected middle cerebral artery. Serial MRI showed the initial high intensity lesion starting on the medial cortex of the temporal lobe, then spreading to throughout the entire temporal lobe. During this period SPECT showed a marked, broad hot spot in the temporal lobe. The medial temporal lobe was high density on the CT 15 days after the onset. As the encephalitic lesion spread more laterally, the hot spot on SPECT moved laterally and then decreased in activity. Eleven weeks after the onset, the MRI showed intracerebral vacuolization of the lesion and it appeared as a wide cold spot on SPECT. The cause of the hot spot seen in the acute period was thought to be vasoparalysis of the affected area rather than breakdown of the blood-brain barrier, or impaired washout of the isotope, because the SPECT images after acetazolamide administration showed the cold spot even in the subacute phase.     

cAMP-dependent phosphorylation of two sites in the alpha subunit of the cardiac sodium channel

The voltage-sensitive Na+ channel is responsible for generating action potentials in the heart which are critical for coordinated cardiac muscle contraction. Cardiac Na+ channels are regulated by cAMP-dependent phosphorylation, but the sites of phosphorylation are not known. Using mammalian cells expressing the rat cardiac Na+ channel (rH1) alpha subunit and site-specific antibodies, we have shown that the alpha subunit of rat heart Na+ channel is phosphorylated selectively by cAMP-dependent protein kinase (PKA) in vitro and in intact cells. Analysis of the sites of phosphorylation by two-dimensional phosphopeptide mapping and site-directed mutagenesis of fusion proteins revealed that the cardiac alpha subunit is phosphorylated selectively in vitro by PKA on Ser526 and Ser529 in the intracellular loop connecting homologous domains I and II (LI-II). These two residues were phosphorylated in intact cells expressing the rH1 alpha subunit when PKA was activated. Our results define a different pattern of phosphorylation of LI-II of cardiac and brain Na+ channels and implicate phosphorylation of Ser526 and Ser529 in the differential regulation of cardiac and brain Na+ channels by PKA.     

The molecular genetics of schizophrenia: an update

OBJECTIVE: This paper aims to summarise the latest molecular genetic findings in schizophrenia, while providing background information on a number of relevant methodological issues. METHOD: Accumulative genetic data indicate that schizophrenia is a genetically complex disease with an unclear mode of transmission. The development and rapid progression of molecular genetics have provided a wide variety of methods to search for genes predisposing to human disease. The genetic basis for a number of the simpler diseases has been identified and characterised using these methods. More recently, progress has been made in identifying genes predisposing to the genetically more complex diseases such as diabetes mellitus, multiple sclerosis, bipolar disorder and schizophrenia. RESULTS: The latest findings on chromosomes 3, 6, 8, 13, 18 and 22 and on the X chromosome are reviewed. CONCLUSIONS: There is now suggestive support for three susceptibility loci (6p24-22, 8p22-21 and 22q12-q13.1) for schizophrenia, and it is likely that other regions will emerge from studies now in progress. Finding and then characterising genes within these loci will require long-term commitment and systematic efforts in clinical, laboratory and analytical fields.     

Inhibition of 5-lipoxygenase diminishes neurally evoked tachykinergic contraction of guinea pig isolated airway

The role of endogenous 5-lipoxygenase products in modulating tachykinergic neurotransmission in guinea pig isolated trachea was investigated. Tachykinin-containing afferent nerve fibers were stimulated with either electrical field stimulation or antidromic stimulation of the right vagus nerve. This resulted in contractions of the isolated caudal trachea and bronchus that could be blocked with either tetrodotoxin or a combination of neurokinin-1 and neurokinin-2 receptor antagonists. The 5-lipoxygenase inhibitor ZD 2138 (1 microM) significantly inhibited these neurally mediated tachykinergic contractions, by approximately 50%, yet had no effect on the contractions evoked by stimulating tachykinergic fibers in an action potential-independent fashion with capsaicin or by exogenously applied neurokinin A. The effect of ZD 2138 on action potential-driven tachykinergic contractions was mimicked by pobilukast, pranlukast, montelukast and zafirlukast, four structurally unrelated antagonists of the cysteinyl leukotriene 1 receptor subtype. Pobilukast had no effect on the tachykinergic contraction in tissues pretreated with ZD 2138. Likewise, ZD 2138 had no effect on the tachykinergic contractions in tissues pretreated with pobilukast. Intracellular electrophysiological recording of the membrane properties of jugular ganglion neurons, the source of tachykinins in the guinea pig trachea/bronchus, demonstrated that leukotriene D4 caused a membrane depolarization of vagal afferent C-fiber neurons and an increase in input impedance, both of which were abolished by zafirlukast. Taken together, these data indicate that in the resting guinea pig isolated trachea/bronchus, endogenous 5-lipoxygenase activity leads to the production of cysteinyl leukotrienes that amplify action potential-dependent release of tachykinins from airway afferent nerve fibers.     

Quality assurance of the dose delivered by small radiation segments

The use of intensity modulation with multiple static fields has been suggested by many authors as a way to achieve highly conformal fields in radiotherapy. However, quality assurance of linear accelerators is generally done only for beam segments of 100 MU or higher, and by measuring beam profiles once the beam has stabilized. We propose a set of measurements to check the stability of dose delivery in small segments, and present measured data from three radiotherapy centres. The dose delivered per monitor unit, MU, was measured for various numbers of MU segments. The field flatness and symmetry were measured using either photographic films that are subsequently scanned by a densitometer, or by using a diode array. We performed the set of measurements at the three radiotherapy centres on a set of five different Philips SL accelerators with energies of 6 MV, 8 MV, 10 MV and 18 MV. The dose per monitor unit over the range of 1 to 100 MU was found to be accurate to within +/-5% of the nominal dose per monitor unit as defined for the delivery of 100 MU for all the energies. For four out of the five accelerators the dose per monitor unit over the same range was even found to be accurate to within +/-2%. The flatness and symmetry were in some cases found to be larger for small segments by a maximum of 9% of the flatness/symmetry for large segments. The result of this study provides the dosimetric evidence that the delivery of small segment doses as top-up fields for beam intensity modulation is feasible. However, it should be stressed that linear accelerators have different characteristics for the delivery of small segments, hence this type of measurement should be performed for each machine before the delivery of small dose segments is approved. In some cases it may be advisable to use a low pulse repetition frequency (PRF) to obtain more accurate dose delivery of small segments.     

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. IV. Alterations in cellular glutathione content

The major goal of this investigation was to determine if the sensitivity of lymphocytes and monocytes to mercury (Hg++) was related to intracellular glutathione (GSH) levels and the thiol redox status [GSH/glutathione disulfide (GSSG)]. To isolate cells based upon their GSH content, T and B-cells were stained with monochlorobimane (MCB) and separated into high and low fluorescent groups by FACS analysis. Cells with high GSH fluorescence were found to be resistant to both the cytotoxic and immunotoxic effects of HgCl2 as evidenced by cell viability and their responsiveness to mitogen, respectively. In contrast, cells with low levels of GSH were extremely sensitive to mercury. To further examine the relationship between GSH level and mercury exposure, T-cells, B-cells and monocytes were treated with different doses of HgCl2 for 12 hrs. All cells exhibited a dose-dependent decrease in GSH content with a concomitant reduction in GSSG levels. However, the GSH/GSSG ratio in these cells remained constant, or increased following exposure to mercury. GSH levels were also reduced in monocytes following exposure to HgCl2; in this case, GSSG levels remained constant and a decline in the GSH/GSSG ratio was observed. For all cell types, mercury did not inhibit the activities of GSH reductase and GSH peroxidase, enzymes responsible for oxidation/reduction of GSH and GSSG, respectively. Results of the study clearly show that susceptibility to the immunotoxic effects of HgCl2 is, in part, dependent upon GSH levels and further that mercury inhibits GSH generation by lymphocytes and monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Types of shear disparity and the perception of surface inclination

A study is reported of (i) the perceived inclination of a textured surface in depth about a horizontal axis as a function of disparity magnitude for horizontal-shear disparity, vertical-shear disparity, and rotation disparity; and (ii) interactions between patterns with shear or rotation disparity and superimposed or adjacent patterns or lines with zero disparity. Horizontal-shear disparity produced strong inclination which was enhanced by superimposed or adjacent zero-disparity stimuli. It produced little or no inclination contrast in superimposed or adjacent zero-disparity stimuli. Vertical-shear disparity produced inclination in the opposite direction (induced effect) which was reduced to near zero by a superimposed zero-disparity pattern. Adjacent vertical-shear and zero-disparity patterns appeared inclined at slightly different angles with a wide curved boundary. This suggests that vertical-shear disparities are averaged over a wide area. Rotation disparity produced minimal inclination. A superimposed or adjacent zero-disparity line appeared strongly inclined. A superimposed or adjacent zero-disparity pattern appeared vertical and caused the pattern with rotation disparity to appear inclined. Four mechanisms are proposed to account for the results: depth contrast, depth enhancement, deformation-disparity processing, and disparity transfer arising from cyclovergence.