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.     

Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain

We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20-35 years) determined using the internal water standard method were (mean+/-SD): [NAA]=10.0+/-3.4 mM (n=53), [tCho]=1.9+/-1.0 mM (n=51), [Cr + PCr]=6.5+/-3.7 mM (n=51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy.     

Reproducibility of functional transcranial Doppler sonography in determining hemispheric language lateralization

BACKGROUND AND PURPOSE: Since functional transcranial Doppler ultrasonography (fTCD) allows convenient and fully automated quantification of language lateralization, it seems ideal for longitudinal studies of perfusion changes during deterioration as well as recovery of language functions. However, during serial examinations, the technical, stochastic, and physiological variabilities of cerebral blood flow velocities (CBFV) have to be considered. Therefore, before fTCD is accepted as a tool for evaluation of changes in lateralization in the diseased state, its reliability in healthy subjects needs to be determined. METHODS: We performed fTCD during a word generation task based on a previously validated technique with automated calculation of the averaged CBFV differences in the middle cerebral arteries providing an index of lateralization (LI). RESULTS: (1) The accuracy of the LI as assessed by the confidence interval was better than 1% of the mean hemispheric difference. (2) On repeated examination, LIs obtained from 10 subjects showed a high test-retest reproducibility (Pearson product moment correlation coefficient r = 0.95, P < 0.0001). (3) On 10 repeated assessments of LI in the same subject, no practice effects were detected. CONCLUSIONS: Functional TCD is a suitable and very robust tool for the longitudinal quantitative measurement of cerebral language lateralization.     

Worries and obsessions in individuals with obsessive-compulsive disorder with and without comorbid generalized anxiety disorder

Participants from the DSM-IV field trial for OCD (N = 381) were divided into two groups based on the SCID interview: those who met current criteria for obsessive-compulsive disorder (OCD) but not generalized anxiety disorder (GAD) and those who met current diagnostic criteria for both. The groups were compared on their severity of obsessive and compulsive symptoms, as well as on the percent of individuals who reported excessive worry concerning everyday issues (e.g. health, finances). The comorbidity rate was 20%. While the presence of GAD did not elevate OCD symptoms per se, it was associated with more pathological responsibility and indecisiveness. Excessive worries were significantly more common in those with comorbid OCD and GAD. The relationship between obsessions and worries is discussed.     

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.     

Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model

Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or both. To investigate the mechanisms of graft rejection, we have developed a canine model of marrow transplantation, which uses DLA-nonidentical unrelated donors in the absence of postgrafting immunosuppression. In this model most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can be facilitated when the recipients are pretreated with monoclonal antibody (MoAb) S5, which recognizes CD44. In this report, we extended these observations by first cloning the canine CD44 and, next, mapping the epitope recognized by S5, which was located in a region conserved among human and canine CD44 and was distinct from the hyaluronan binding domain. However, in vitro binding of S5 caused a conformational change in CD44, which allowed increased hyaluronan binding. Then, we reexamined the in vivo model of marrow transplantation and compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The enhanced in vivo effect was not related to differences in the MoAbs' avidities, since both S5 and IM7 had equivalent binding to CD44, but most likely related to the specific epitope that S5 recognizes. Thus, this study shows that the effect of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one cannot assume that any anti-CD44 would work.     

Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication

Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.     

Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants

The effects of mechanical injury on the metabolism of cartilage matrix are of interest for understanding the pathogenesis of osteoarthrosis and the development of strategies for cartilage repair. The purpose of the present study was to examine the effects of injury on matrix turnover in a calf articular cartilage explant system for which the effects of mechanical loading on cell activity and the cell-mediated pathways of matrix metabolism are already well characterized. New methods of quantitative autoradiography were used in combination with established biochemical and biomechanical techniques for the analysis of cell and matrix responses to acute mechanical injury, with particular attention to the processes of localized matrix turnover in the cell-associated matrices of individual chondrocytes. Matrix deposition and turnover around cells in control explants was spatially dependent, with the highest rates of proteoglycan deposition and turnover and the lowest rates of collagen deposition (as indicated by [3H]proline autoradiography) occurring in the pericellular matrix. Injurious compression was associated with (a) an abrupt decrease in the tensile load-carrying capacity of the collagen matrix, apparently associated with mechanical failure of the tissue, (b) a considerable but subtotal decrease in cell viability, marked by the emergence of an apparently inactive cell population interspersed within catabolically active but abnormally large cells, and (c) sustained, elevated rates of proteoglycan turnover, particularly in the cell-associated matrices of apparently viable cells, which involved the increased release of aggregating species in addition to a spectrum of degradation fragments that were also in controls. These results may represent an in vitro model for the responses of chondrocytes and the cartilage extracellular matrix to mechanical injury.     

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.