7Li nuclear magnetic resonance study for the determination of Li+ properties in neuroblastoma SH-SY5Y cells

Lithium has been used clinically in the treatment of manic depression. However, its pharmacologic mode of action remains unclear. Characteristics of Li+ interactions in red blood cells (RBCs) have been identified. We investigated Li+ interactions on human neuroblastoma SH-SY5Y cells by developing a novel 7Li NMR method that provided a clear estimation of the intra- and extracellular amounts of Li+ in the presence of the shift reagent thulium-1,4,7,10-tetrazacyclododecane-N,N',N',N'-tetramethylene phosphonate (HTmDOTP4-). The first-order rate constants of Li+ influx and efflux for perfused, agarose-embedded SH-SY5Y cells in the presence of 3 mM HTmDOTP4- were 0.055 +/- 0.006 (n = 4) and -0.025 +/- 0.006 min(-1) (n = 3), respectively. Significant increases in the rate constants of Li+ influx and efflux in the presence of 0.05 mM veratridine indicated the presence of Na+ channel-mediated Li+ transport in SH-SY5Y cells. 7Li NMR relaxation measurements showed that Li+ is immobilized more in human neuroblastoma SH-SY5Y cells than in human RBCs.     

Autonomic paroxysms: their pathogenesis, diagnosis and treatment

In the article the rules about etiology and pathogenesis of vegetative paroxysms are stated based on careful analysis of the publications of researches as Russian, so foreign authors, and also own experimental and clinical supervision. During experimental and clinical researches the modern methods were used, enabling to estimate from positions of the system analysis different parts of pathogenesis of vegetative paroxysms, and also to offer ways of differential diagnostics of the various forms of disease. The application of some new preparations and direction of therapy of vegetative paroxysms are substantiated, and also the various circuits of treatment of the patients with distinguishing forms of given pathology are motivated.     

Role of cadherins in the transendothelial migration of melanoma cells in culture

This study examines the nature and extent of the relationship between stress levels and intentions to participate in a worksite smoking cessation program among male current smokers (n = 220) employed in an automobile manufacturing plant. A plantwide survey was conducted which measured job stress, nonjob stress, smoking behavior, and intent to participate. The results of polychotomous logistic regressions suggest that among the current smokers in this plant, job and nonjob stress were positively associated with workers' intentions to participate in a worksite smoking cessation program. Thus, contrary to the popular notion that stress diminishes the motivation to quit, employees under high levels of stress may be most receptive to educational interventions intended to persuade smokers to commit to quitting.     

Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin

Glycoprotein 330 (gp330) is a member of a family of endocytic receptors related to the low density lipoprotein receptor. gp330 has previously been shown to bind a number of ligands in common with its family member, the low density lipoprotein receptor-related protein (LRP). To identify ligands specific for gp330 and relevant to its localization on epithelia such as in the mammary gland, gp330-Sepharose affinity chromatography was performed. As a result, a 70-kDa protein was selected from human milk and identified by protein sequencing to be apolipoprotein J/clusterin (apoJ). Solid-phase binding assays confirmed that gp330 bound to apoJ with high affinity (Kd = 14.2 nM). Similarly, gp330 bound to apoJ transferred to nitrocellulose after SDS-polyacrylamide gel electrophoresis. LRP, however, showed no binding to apoJ in either type of assay. The binding of gp330 to apoJ could be competitively inhibited with excess apoJ as well as with the gp330 ligands apolipoprotein E, lipoprotein lipase, and the receptor-associated protein, a 39-kDa protein that acts to antagonize binding of all known ligands for gp330 and LRP. Several cultured cell lines that express gp330 and ones that do not express the receptor were examined for their ability to bind and internalize 125I-apoJ. Only cells that expressed gp330 endocytosed and degraded radiolabeled apoJ. Furthermore, F9 cells treated with retinoic acid and dibutyryl cyclic AMP to increase expression levels of gp330 displayed an increased capacity to internalize and degrade apoJ. Cellular internalization and degradation of radiolabeled apoJ could be inhibited with unlabeled apoJ, receptor-associated protein, and gp330 antibodies. The results indicate that gp330 but not LRP can bind to apoJ in vitro and that gp330 expressed by cells can mediate apoJ endocytosis leading to lysosomal degradation.     

Promyelocytic blast crisis of chronic myelogenous leukaemia with translocations (9;22) and (15;17)

The murine monoclonal antibody A7 (MAb A7) is reactive against most human gastric cancer cell lines. Using a nude mouse peritoneal dissemination model of human gastric cancer, we investigated targeted chemotherapy using a conjugate of neocarzinostatin (NCS) with MAb A7 (A7-NCS). After demonstrating cytotoxicity of the complex against the human gastric cancer cell line MKN45 in vitro, we intraperitoneally injected A7-NCS, NCS or saline into nude mice bearing peritoneally disseminated human gastric cancer. A7-NCS inhibited peritoneal dissemination significantly more effectively than NCS. MAb A7 may prove to be an effective carrier for antineoplastic drugs in patients with peritoneal dissemination of gastric cancer.     

Membrane CD45R isoform exchange on CD4 T cells is rapid, frequent and dynamic in vivo

CD4 T cells bearing high (240-190 kDa) and low (180 kDa) molecular mass isoforms of the leukocyte common antigen CD45 define functionally distinct subsets which have been equated with naive and memory T cells. In the rat, CD4 T cells expressing a high molecular mass isoform [identified by monoclonal antibody MRC-OX22 (anti-CD45RC)] exchange this for the 180 kDa molecule (CD45RC-) when stimulated by antigen. Here we show, by transferring mature allotype-marked CD45RC- CD4 T cells (depleted of immature Thy-1+ CD45RC- recent thymic emigrants) into normal euthymic recipients, that many T cells re-express the high molecular mass isoform in less than 6 h. By 24 h, 30-60% of CD45RC- CD4 T cells became CD45RC+; within a week the entire cohort appeared to exchange the low for the high molecular mass isoform. Isoform exchange was dynamic and many CD4 T cells returned once again to the CD45RC- state. CD45RC- CD4 T cells declined in number more rapidly than the CD45RC+ subset after transfer. The results suggest that CD45R isoforms distinguish between resting T cells (CD45RC+) and those which have encountered antigen in the recent past. CD45R isoforms would appear to be unsuitable markers of naive and memory T cells.     

A technique for fractionated stereotactic radiotherapy in the treatment of intracranial tumors

PURPOSE: The excellent treatment results obtained with traditional radiosurgery have stimulated attempts to broaden the range of intracranial disorders treated with radiosurgical techniques. For major users of radiosurgery this resulted in a gradual shift from treating vascular diseases in a single session to treating small, well delineated primary tumors on a fractionated basis. In this paper we present the technique currently used in Montreal for the fractionated stereotactic radiotherapy of selected intracranial lesions. METHODS AND MATERIALS: The regimen of six fractions given every other day has been in use for "fractionated stereotactic radiotherapy" in our center for the past 5 years. Our current irradiation technique, however, evolved from our initial method of using the stereotactic frame for target localization and first treatment, and a "halo-ring" with tattoo skin marks for the subsequent treatments. Recently, we developed a more precise irradiation technique, based on an in-house-built stereotactic frame which is left attached to the patient's skull for the duration of the fractionated regimen. Patients are treated with the stereotactic dynamic rotation technique on a 10 MV linear accelerator (linac). RESULTS: In preparation for the first treatment, the stereotactic frame is attached to the patient's skull and the coordinates of the target center are determined. The dose distribution is then calculated, the target coordinates are marked onto a Lucite target localization box, and the patient is placed into the treatment position on the linac with the help of laser positioning devices. The Lucite target localization box is then removed, the target information is tattooed on the patient's skin, and the patient is given the first treatment. The tattoo marks in conjunction with the target information on the Lucite target localization box are used for patient set-up on the linac for the subsequent 5 treatments. The location of the target center is marked with radio-opaque markers on the target localization box and verified with a computerized tomography scanner prior to the second treatment. The same verification is done prior to other treatments when the target center indicated by the target localization box disagrees with that indicated by the tattoo marks. The new position of the target center is then determined and used for treatment positioning. CONCLUSION: The in-house-built frame is inexpensive and easily left attached to the patient's skull for the 12 day duration of the fractionated regimen. Positioning with the Lucite target localization box verified with tattoo marks ensures a high level of precision for individual fractionated treatments.     

The striatum in the system of the central mechanisms of biorhythm control

BACKGROUND: This study was undertaken to assess the safety and efficacy of a treatment involving brief counseling and the nicotine patch among hospital inpatients and to identify variables associated with long-term smoking cessation following hospitalization. METHODS: One hundred eighty-five patients were randomly assigned to one of three smoking cessation interventions: (1) A Minimal Care (MC) condition, consisting of a brief physician-delivered motivational message to stop smoking, (2) a Counseling + Active Nicotine Patch (CAP) condition in which patients received the motivational message, a 6-week supply of nicotine patches, and extended bedside and telephone counseling, and (3) a Counseling + Placebo Patch (CPP) condition identical to the CAP condition except the supplied patches contained no nicotine. RESULTS: At 6-month follow-up, abstinence rates for the three treatments were 4.9, 6.5, and 9.7% for the MC, CPP, and CAP treatments, respectively. These differences were not statistically significant. Patients admitted for respiratory disease were more likely to quit than patients with any other diagnosis. The nicotine patch was well tolerated by hospital inpatients. CONCLUSIONS: The initiation of nicotine patch therapy during hospitalization appears to be safe when used among patients carrying a wide range of diagnoses. Our study provided no evidence of the superiority of nicotine patches versus placebo, but this does not preclude the possibility that future research using larger samples might detect differences between patch groups. Hospital interventions for smoking cessation may be most effective among patients hospitalized for a smoking-related illness such as respiratory disease.     

Liz1p, a novel fission yeast membrane protein, is required for normal cell division when ribonucleotide reductase is inhibited

Ribonucleotide reductase activity is required for generating deoxyribonucleotides for DNA replication. Schizosaccharomyces pombe cells lacking ribonucleotide reductase activity arrest during S phase of the cell cycle. In a screen for hydroxyurea-sensitive mutants in S. pombe, we have identified a gene, liz1(+), which when mutated reveals an additional, previously undescribed role for ribonucleotide reductase activity during mitosis. Inactivation of ribonucleotide reductase, by either hydroxyurea or a cdc22-M45 mutation, causes liz1(-) cells in G2 to undergo an aberrant mitosis, resulting in chromosome missegregation and late mitotic arrest. liz1(+) encodes a 514-amino acid protein with strong similarity to a family of transmembrane transporters, and localizes to the plasma membrane of the cell. These results reveal an unexpected G2/M function of ribonucleotide reductase and establish that defects in a transmembrane protein can affect cell cycle progression.