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M A Russell

Publications and source records attributed to M A Russell.

At least 37 records · Page 2Linked to original sources
PubMed1997

Transglutaminase II: a new class of GTP-binding protein with new biological functions.

Tissue type transglutaminase (TGase II) is historically a member of the transglutaminase family, which covalently cross-links cellular proteins and polyamines. A recent new finding in the TGase II field is that the enzyme functions as a signal mediator from receptors to an effector in transmembrane signaling. This review will discuss the recent development of TGase II. This new signal transducer was termed Gh when initially discovered and was recently found to be TGase II. To help the reader understand the role of Gh as a signal mediator, the role of heterotrimeric G-proteins in hormone-mediated transmembrane signaling is briefly discussed. We have highlighted how Gh transmits the alpha 1-adrenoceptor signal to the phospholipase C-delta 1 and how Gh is activated and deactivated compared to the prototype of heterotrimeric G-proteins. Recent developments regarding the structure-function of Gh and other biological functions of Gh are discussed to facilitate understanding the impact of Gh in cells.

Animals↗
PubMed1997

Nicotine enemas for active ulcerative colitis--a pilot study.

BACKGROUND: Since transdermal nicotine is of value in the treatment of active ulcerative colitis but is often associated with side-effects, an alternative in the form of topical therapy with nicotine enemas has been developed. METHODS: In an open study, 22 patients with active colitis, all non-smokers, were asked to take a 100 mL enema containing 6 mg of nicotine every night for 4 weeks. Pre-trial treatment using mesalazine (n = 16), oral prednisolone (8), cyclosporin (1) and azathioprine (1) was kept constant for the month prior to assessment and during the study period. Symptoms, with stool frequency, were recorded on a diary card and an endoscopy was performed with rectal biopsy at the beginning of the study and after 4 weeks. RESULTS: Seventeen of the 22 patients completed 1 month of treatment. Mean duration of relapse was 29 weeks, range 3-94. Sixteen of 17 improved their St Mark's score. Urgency and stool frequency improved in 12 patients, sigmoidoscopic and histological scores in 10. Three patients had a full remission of symptoms with normal sigmoidoscopy. Six of 10 with a partial response continued with the enemas for a second month and five showed further improvement with full remission in two. The enema appeared effective when added to conventional treatment and produced few side-effects. CONCLUSION: Topical nicotine therapy for ulcerative colitis may have a place in future management, but controlled studies are needed.

Adult↗
PubMed1997

Smoking, alcohol consumption, and leukocyte counts.

Blood was collected from 684 healthy volunteers and examined for total and differential white blood cell (WBC) counts. A subgroup also was tested for numbers of T cells, B cells, and CD4 and CD8 subsets. Smoking status and alcohol consumption were determined by means of questionnaire, and smoking status was verified with serum cotinine concentration. High smoking rate was associated with increases in all counts. Former smokers abstinent less than 5 years still demonstrated elevated counts, whereas those abstinent more than 5 years had WBC counts comparable to those in persons who were never smokers. Compared with levels in those who had never smoked, total WBC counts were 27% higher in current smokers and 14% higher in former smokers who were abstinent for less than 5 years. Lymphocyte counts were 9% higher in those consuming more than one alcoholic drink per day than in those consuming less alcohol, but drinking was not associated with other cell populations.

Adult↗
PubMed1997

Effect of nicotine on large bowel mucus thickness, eicosanoids and faecal proteinase in ferrets.

BACKGROUND: Following observations on the effect of subcutaneous nicotine on rectal mucosal eicosanoids and mucus in the rabbit we have repeated the work in ferrets which may be a more suitable animal model. AIMS AND METHODS: The effect of nicotine on mucosal eicosanoids, the adherent mucus layer, and faecal proteinases in the large bowel of ferrets was examined in forty animals randomly allocated to five groups, a control and four treatment groups. They were given subcutaneous saline or nicotine via an Alzet pump in doses of 0.3, 0.6, 1.2 and 2.0 mg/kg/day for 10 days and then sacrificed; measurements were made of serum nicotine and cotinine levels, rectal mucosal eicosanoids, adherent rectal and colonic mucus thickness, and faecal proteinases. RESULTS: No significant differences were observed for any measurements, except for serum nicotine and cotinine levels, which were raised consistent with the dose given. CONCLUSION: Nicotine had no effect on measurements, which may possibly be important in the relationship between smoking and ulcerative colitis.

Animals↗
PubMed1997

Effect of haloperidol on nicotine-induced enhancement of vigilance in human subjects.

We posed the question whether the cognitive enhancement caused by nicotine in human subjects is mediated by dopamine (DA) release. This issue was addressed by testing performance in the Wesnes and Warburton vigilance task after s.c. nicotine with or without concomitant oral haloperidol. The subjects were moderate (10-14 cigarettes/day) smokers after overnight deprivation of smoking. After an initial practice session, each subject participated in four further sessions spread over 2 weeks, after: placebo/placebo, placebo/haloperidol (5 mg), placebo/nicotine (0.8 mg) or nicotine/haloperidol, double-blind with a balanced ordering of drug combinations. On each occasion, performance was measured on the vigilance task, a finger tapping test, and digit span forward and backward. Nicotine improved detection sensitivity on the vigilance task, and this effect was unchanged by haloperidol; the latter compound reduced forward digit span. Thus, the improved vigilance caused by nicotine does not appear to be mediated by DA systems.

Adolescent↗
PubMed1996

Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers.

In a double-blind placebo-controlled crossover study the effects of two doses of subcutaneous nicotine and saline were compared on a range of performance measures in 18 abstaining smokers and 18 never-smokers. Each subject received two injections (40 min apart) of saline, 0.3 mg nicotine, or 0.6 mg nicotine in a balanced order over three sessions. Performance was assessed before and after the injections on nine tests [news recall, Sternberg memory task, finger tapping, logical reasoning, rapid visual information processing (RVIP), long-term word recognition, digit recall, Stroop test, and critical flicker fusion threshold]. In the abstinent smokers, nicotine produced significantly faster correct responses on the logical reasoning test, more target hits, faster reaction times and improved sensitivity on the RVIP task, and more correct responses on word recognition. In never-smokers, nicotine produced faster reaction times on the RVIP and digit-recall tasks, although in the latter case this was at the expense of fewer correct responses. There were no significant differences between the two groups' responses to nicotine but smokers performed worse than never-smokers prior to injections, even controlling for background characteristics. These results are consistent with other recent research suggesting a primary effect of nicotine in enhancing cognitive performance.

Adult↗
PubMed1996

Effects of nicotine and amphetamine on latent inhibition in human subjects.

Latent inhibition (LI) is a phenomenon in which repeated non-reinforced exposure to a stimulus retards subsequent conditioning to that stimulus; it reflects a process whereby irrelevant stimuli become ignored, and has been the subject of study concerning attentional abnormalities in schizophrenia. Low doses of the indirect dopamine (DA) agonists, amphetamine and nicotine, disrupt LI in the rat. These drugs are believed to disrupt LI via DA release in the nucleus accumbens; LI in amphetamine- and nicotine-treated rats is reinstated by administration of the DA antagonist haloperidol. In human subjects, low doses of amphetamine abolish LI, and more recently haloperidol has been shown to potentiate LI. The present study investigated the effects of nicotine on LI in human subjects, and also attempted to replicate the abolition of LI by amphetamine. Nicotine failed to affect LI when administered either subcutaneously or by cigarette smoking. LI was, however, abolished in a group of subjects given 5 mg amphetamine 90 min before testing. Supplementary analyses of the data pooled from all three experiments showed that, in contrast to an earlier report, LI was no weaker in smokers than in nonsmokers.

Adult↗
PubMed1996

Managing law enforcement (K-9) dog bites in the emergency department.

OBJECTIVE: To review the types of injuries due to law enforcement (K-9) dog bites and address related management issues. METHODS: A case series of law enforcement dog bite victims is reported and related literature reviewed. RESULTS: Law enforcement dogs are taught a bite-and-hold technique for subduing individuals suspected of felony crimes. This bite-and-hold technique's greater applied force results in a unique spectrum of injuries, including deep puncture wounds, severe crush injuries, large tissue avulsions and lacerations, wounds necessitating surgical débridement, bony injuries ranging from cortical violations to displaced fractures, neurovascular damage, and other wounds at high risk for infection. The four reported cases highlight the types of injuries and complications associated with law enforcement dog bites. CONCLUSION: Attention to potential deep injuries of nerves, vessels, and the musculoskeletal system is essential with law enforcement dog bites. Injuries associated both with pursuit and arrest and with the bites themselves must be identified and assessed. Guidelines for the ED treatment of patients with law enforcement dog bite injuries are proposed.

Adolescent↗
PubMed1996

Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of non-smokers. Previous controlled trials have shown benefit with transdermal nicotine when given with 5-aminosalicylic acid in active disease but not when given alone as maintenance therapy. OBJECTIVE: To examine nicotine alone compared with prednisolone in active disease. PATIENTS AND METHODS: Sixty-one patients with active ulcerative colitis were treated with either transdermal nicotine patches or 15 mg prednisolone for 6 weeks in a randomized, double-blind study. Incremental doses of nicotine were given for the first 9 days; patients tolerated between 15 and 25 mg daily. Most patients were taking mesalazine at entry which was discontinued at day 10; a few were taking topical steroids which were discontinued at the onset. Clinical, sigmoidoscopic and histological assessments were made at baseline and 6 weeks, or at premature withdrawal. Symptoms were recorded on a diary card, and the clinician made a global clinical assessment. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Forty-three patients completed the 6-week trial; of these, 6 of 19 in the nicotine group achieved full sigmoidoscopic remission compared with 14 of 24 with prednisolone (P = 0.08). In those who completed the 6-week study, there was significant improvement within both the nicotine and prednisolone group for the St Mark's score (P < 0.05 and P < 0.01, respectively), Global Clinical Grade (P < 0.01 for both), blood in the stool (P < 0.05 and P < 0.01), abdominal pain (P < 0.05 and P < 0.01) and sigmoidoscopic score (P < 0.01 and P < 0.001); differences between groups tend to favour prednisolone, but none reach statistical significance. However, on intention-to-treat analyses there is little clear evidence of improvement in either group apart from sigmoidoscopic score in which prednisolone was associated with a significantly greater improvement than nicotine (P < or = 0.05). The nicotine group had more withdrawals than the prednisolone group, 11 versus 7, respectively (P = 0.23), both for deterioration (6 vs. 5) and side effects (5 vs. 2, P = 0.15). Side effects were more frequently reported in the nicotine group (average 1.47 episodes per person) than the prednisolone group (average 0.61; P = 0.03), the most common of which were nausea, light-headedness and tremor. CONCLUSION: In those who managed to complete the 6-week study, nicotine alone appeared to be of only very modest benefit in acute colitis and was not as effective as 15 mg of prednisolone daily.

Administration, Cutaneous↗
PubMed1995

Allosteric regulation of [3H]vinblastine binding to P-glycoprotein of MCF-7 ADR cells by dexniguldipine.

Plasma membranes were prepared from the P-glycoprotein expressing human breast cancer cell line MCF-7 ADR. [3H]Vinblastine bound to these membranes saturably with a Bmax of 24 pmol/mg of protein and KD of 23 nM. In contrast, membranes from the parent cells MCF-7 WT, which do not express P-glycoprotein, did not bind [3H]vinblastine with high affinity. Cytotoxics known to be transported by P-glycoprotein inhibited the binding of [3H]vinblastine, as did multidrug reversing agents including the 1,4-dihydropyridine, dexniguldipine-HCl (Ki, 15 nM). In dissociation kinetic experiments, dexniguldipine-HCl accelerated the dissociation of [3H]vinblastine from P-glycoprotein, indicating a negative heterotropic allosteric mechanism of action through a drug binding site distinct from that of vinblastine. Other 1,4-dihydropyridines tested also accelerated [3H]vinblastine dissociation from P-glycoprotein, however, multidrug reversing drugs of different chemical classes, including quinidine, verapamil and cyclosporin A did not. These results suggest that P-glycoprotein of MCF-7 ADR cell membranes possesses at least two drug acceptor sites which are allosterically coupled: receptor site-1 which binds vinca alkaloids, and receptor site-2 which binds 1,4-dihydropyridines such as dexniguldipine-HCl, which had the highest affinity of the tested derivatives.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Transdermal nicotine as maintenance therapy for ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Having found previously that treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission. METHODS: We treated 80 patients with ulcerative colitis in remission with either transdermal nicotine or placebo patches for six months in a randomized, double-blind study. Incremental doses of nicotine were given for the first three weeks to achieve a maintenance dose; most patients tolerated 15 mg for 16 hours daily. All patients were taking mesalamine preparations as maintenance treatment at entry into the study; this treatment was stopped once the maintenance dose of nicotine was achieved. Clinical, sigmoidoscopic, and histologic assessments were made at the beginning and the end of the study, or at relapse. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: There was no significant difference in the number of relapses between the groups. Twenty-two patients in the nicotine group were prematurely withdrawn from the study, 14 because of relapse and 8 for other reasons, including side effects and protocol violations. In the placebo group, 20 patients were withdrawn prematurely, 17 because of relapse and 3 for other reasons. Among patients using 15-mg nicotine patches, serum nicotine and cotinine concentrations were lower than expected and may reflect poor compliance. Side effects were reported by 35 patients--21 in the nicotine group and 14 in the placebo group--the most common of which were nausea, lightheadedness, and itching. CONCLUSIONS: Transdermal nicotine alone was no better than placebo in the maintenance of remission of ulcerative colitis, and premature withdrawal due to side effects was more common in the nicotine group.

Administration, Cutaneous↗
PubMed1995

Nicotine intake in smokers increases following a single dose of haloperidol.

The effects of oral haloperidol on nicotine intake, subjective measures of craving and smoking satisfaction were compared with placebo in light-to-moderate smokers from a post-prandial cigarette and during the subsequent hour of unrestricted smoking. Subjects smoked significantly more, as measured by blood nicotine levels, when they had received haloperidol, although there was no difference between haloperidol and placebo on any subjective measures. These findings may be interpreted to reflect a compensatory increase in smoking in order to obtain the usual nicotine reward. Having achieved usual levels of reward, subjects did not experience a decrease in subjective measures of smoking satisfaction or an increase in nicotine craving.

Adult↗
PubMed1995

Naltrexone, smoking behaviour and cigarette withdrawal.

In order to examine the role of endogenous opioids in the reinforcing effects of nicotine, a double-blind, placebo-controlled, cross-over design was used to study the effects of the opiate antagonist, naltrexone, on smoking behaviour and cigarette withdrawal in 12 heavy smokers. Although naltrexone (50 mg) appeared to reduce the perceived difficulty of abstaining during 24-h cigarette withdrawal, other withdrawal symptoms were unaffected. Naltrexone also had no effect on a variety of biochemical and behavioural measures of nicotine intake or on subjective satisfaction and enjoyment from the first cigarette smoked after 24-h abstinence. Similarly naltrexone (100 mg) had no effect on smoking behaviour, nicotine intake or satisfaction from smoking during a 48-h period of ad libitum smoking. However, during the ad libitum smoking period naltrexone caused mood changes of the kind that occur during tobacco withdrawal. Since nicotine intake and smoking behaviour were unaffected, the mood changes are unlikely to have been mediated by blockade or any other form of opioid interaction with nicotinic mechanisms. These findings provide evidence against the notion that the endogenous opioids are involved in mediating the reinforcing properties of nicotine in smokers under normal conditions.

Adult↗
PubMed1995

Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice.

The transdermal nicotine patch has proved an effective aid to smoking cessation. The ease of securing good compliance gives it a potential advantage over nicotine gum as an adjunct to brief advice and support in primary care settings where the major public health impact is obtained. In a preliminary report of half the sample of a randomized placebo controlled trial, we showed the patch to be effective in a general practice setting. We report here the definitive results of the full sample, including dose effects, predictors of outcome and other issues of theoretical and practical interest. A total of 1200 heavy smokers (> or = 15 per day), attending 30 general practices in 15 English counties received brief GP advice, a booklet and 16 hours per day patch treatment for 18 weeks. Dose increase and abrupt vs. gradual reduction of patch dosage were also randomized and follow-ups conducted at 1, 3, 6, 12, 26 and 52 weeks. Outcome was measured by self-reported complete abstinence from week 3 to 52 with biochemical validation at all follow-up points. Nicotine patch treatment doubled the rate of continuous abstinence up to 1 year (nicotine 9.6%, placebo 4.8%, p < 0.01); it most likely worked by reducing withdrawal symptoms. It enhanced cessation during the first week and reduced relapse during the second week. The dose increase after week 1 produced no sustained increase in cessation. Gradual reduction was no better at preventing relapse than abrupt withdrawal of patches after week 12. Whether relapse would have increased by ending treatment at some point between weeks 3 and 12 was not tested. Although pre-treatment dependence on cigarettes was prognostic of failure, the patches were equally helpful to both highly and less dependent smokers. Patches were particularly helpful to smokers with pre-treatment subclinical dysthymic symptoms. All but one of the 96 subjects eventually achieving long-term abstinence in the study quit during the first week of cessation.

Administration, Cutaneous↗
PubMed1995

Safety in bullet recovery procedures: a study of the Black Talon bullet.

Bullets or bullet fragments that are recovered during forensic autopsy and examined later as evidence may present hazards to both pathologists and forensic scientists due to sharp edges or jagged projections created by the deformation or fragmentation of a bullet upon impact with its target. The recent introduction of the Black Talon bullet has increased this hazard by its design, which produces a controlled expansion upon target impact that raises six harp edges from its copper jacket. We describe the appearance of the bullet along with methods for detection and recovery that can be applied as universal precautions of safe bullet handling.

Firearms↗
PubMed1995

Analysis of an enhancer trap expressed in regenerating Drosophila imaginal discs.

In Drosophila, imaginal discs are the undifferentiated larval precursors of the pattern of epidermal and sensory neural cells in each adult segment. Although cell fates are already specified by late third instar, disc fragments can either regenerate or duplicate after growth in culture. The outcome depends on signaling between cells across the healed wound and involves a redeployment of the expression patterns of selector genes and other disc pattern genes. We recently used the enhancer-trap method to screen for such genes that are expressed ectopically at the wound-heal site in imaginal discs undergoing regeneration. Here we report the cloning by plasmid rescue of transcribed sequences adjacent to one such enhancer-trap insertion. Using Northern analysis and in situ hybridization we show that one transcript is expressed in the embryo and in imaginal discs in a pattern similar to that of the enhancer trap. We also, by imprecise excision of the enhancer-trap insertion, generated a series of flanking deletions that were mapped using Southern analysis and complementation.

Animals↗
PubMed1995

Interactions between hydroxocobalamin and nitric oxide (NO): evidence for a redox reaction between NO and reduced cobalamin and reversible NO binding to oxidized cobalamin.

Interactions of nitric oxide (NO) with various cobalamin species have been examined, apparently for the first time, with both absorption and electron paramagnetic resonance spectroscopy. Only slight shifts in the absorption spectrum of hydroxocobalamin, B12a [Cb(III)], were produced by NO, but dramatic changes in the spectrum of B12r [Cb(III)] were found on addition of NO. The addition of NO shifted the spectrum of Cb(II) to one very similar to that of Cb(III), indicating the oxidation of Cb(II). The addition of NO to Cb(III) resulted in a novel, weak and previously undescribed electron paramagnetic resonance signal. Although it has not been fully characterized, this appears to represent a reversible complex in which NO is liganded to the Cb(III). When NO was added to Cb(II), its strong electron paramagnetic resonance spectrum was replaced by that of this novel species, consistent with oxidation of Cb(II) by NO and then binding of additional NO by the resulting Cb(III). Porcine, aortic endothelial cells were able to partially reduce Cb(III), and release to the supernatant a previously characterized superoxide cobalt(III) complex, but some Cb(II) remained with the cell fraction. These reactions of Cb species could play a role in altering intracellular and intratissue levels of NO.

Animals↗