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Biomedical subjects

J H Robinson

Publications and source records attributed to J H Robinson.

At least 55 records · Page 3Linked to original sources
PubMed1997

T-Cell epitope mapping the PorB protein of serogroup B Neisseria meningitidis in B10 congenic strains of mice.

T-cell epitope mapping the meningococcal serotype 15 PorB protein performed in this study in three congenic strains of mice with B10 genetic background revealed at least three murine T-cell epitopes (55-72, 163-180, and 226-261), located in the highly conserved putative transmembrane regions of Neisserial porins. Proliferation assays with popliteal lymph node cells derived from mice immunized with the PorB protein or with synthetic 18-mer peptides showed that epitope 163-180 immunized only in the H-2d haplotype, epitope 55-72 could be presented by both H-2f and H-2s molecules, while the 226-261 region covered by three overlapping peptides could be efficiently recognized in context of all three MHC class II haplotypes studied. Inhibition experiments with blocking I-Aalpha- and I-Ealpha-specific mAb showed that peptide 163-180 was presented by I-Ad and peptide 244-261 was presented by both I-Af and I-As. In addition, evidence was obtained that peptide 226-243 was presented in context of H-2d or I-As haplotypes and peptide 55-72 was presented in context of I-Af and I-As loci. Finally, the Norwegian outer membrane vesicle vaccine, but not the purified PorB protein, could recall responses in mice immunized with synthetic peptides corresponding to the 226-261 region. Altogether, these results suggest that T-cell epitopes identified on the serotype 15 PorB protein, particularly those presented by several MHC class II molecules (e.g., 226-261), could have important implications for the development of meningococcal vaccines.

Amino Acid Sequence↗
PubMed1997

Hierarchy of SPEA presentation to T cells by mouse MHC haplotypes.

The ability of splenic antigen-presenting cells (APC) from nine independent mouse major histocompatibility complex (MHC) haplotypes to present recombinant streptococcal exotoxin A (rSPEA) to heterogeneous T cells and mouse T cell clones were compared using proliferation assays. We report that there is marked variation between MHC haplotypes, which can be ranked as follows: H2z > H2s = H2f = H2p = H2r = H2k > H2d > H2b = H2q. In some haplotypes both A and E molecules bind rSPEA with low affinity. In addition, we show that presentation is preferentially by E molecules in haplotypes where A and E are coexpressed, but that A alleles also bind and present rSPEA, based on inhibition of responses by anti-E and anti-A mAbs. Furthermore, using strains of mice which fail to express E, we demonstrate that A(s) and Af present rSPEA with high efficiency, whereas Aq and Ab are the least efficient of all haplotypes. The results suggest that there is significant variation in the ability of different alleles of both E and A molecules to bind and present rSPEA.

Animals↗
PubMed1996

Faster P300 latency after smoking in visual but not auditory oddball tasks.

In two separate experiments, P300 was recorded from overnight-abstaining smokers before and after smoking. In the first experiment, 32 subjects counted forward by ones and counted backwards by threes upon presentation of a rare tone burst (20%) in a stream of standard tones. There were no changes in P300 amplitude or latency pre- to post-smoking (1.1-mg FTC nicotine-yield cigarette). In the second experiment, 29 subjects completed auditory and visual oddball tasks before smoking, after smoking a low nicotine-yield cigarette (0.05 mg), after smoking a higher nicotine-yield cigarette (1.1-mg), and after smoking a second 1.1-mg cigarette. In the visual oddball task, P300 latency decreased after smoking the first higher-yield cigarette relative to both pre-smoking and post smoking the lower-yield cigarette. This effect was maintained after smoking the second higher-yield cigarette. In the visual task, P300 amplitude increased after smoking the first higher-yield cigarette (from a lower baseline level) in a group of subjects with larger changes in tidal-breath CO but not in a group with smaller changes in CO. There were no effects of smoking on P300 amplitude or latency in the auditory tasks of either the first or second experiment.

Adult↗
PubMed1996

Examining the relation between usual-brand nicotine yield, blood cotinine concentration and the nicotine- "compensation" hypothesis.

Eight data sets relating usual-brand nicotine yield (FTC method or equivalent) to blood cotinine concentration are reviewed with respect to the so-called nicotine-"compensation" hypothesis, i.e., that all smokers achieve a specific level of nicotine in their blood, regardless of the FTC nicotine yield of the cigarette smoked. The data from the studies reviewed here indicate wide variability in blood cotinine concentrations over the range of FTC nicotine yields and that the nicotine-compensation hypothesis is not supported. On average, blood cotinine concentrations are found to be roughly midway between complete compensation (all smokers absorb equal amounts of nicotine regardless of FTC nicotine yield) and the value expected if there was no compensation (i.e., smokers absorb an amount of nicotine exactly equal to the FTC yield). As a result of individual smoking-behavior differences (number of cigarettes smoked, puff volume, puff frequency inhalation volume and depth, etc.), the data indicate that, on average, smokers achieve roughly 50% lower blood cotinine concentrations than predicted by the nicotine-compensation hypothesis.

Cotinine↗
PubMed1996

Assessing the sensory role of nicotine in cigarette smoking.

Thirty-two subjects were tested in five double-blind sessions (16 subjects in the morning following overnight smoking abstention, and 16 in the afternoon following ad-lib smoking). In each session, subjects smoked one of five experimental (EX) cigarettes having the following FTC nicotine/"tar' yields in mg: 0.08/8.5, 0.17/9.1, 0.37/9.8, 0.48/9.8, and 0.74/10.4. In a sixth session, subjects smoked a 0.71/8.6 commercial "light' (CL) cigarette that was their usual brand. Before and after smoking, subjects subjectively rated their desire to smoke a cigarette of their usual brand and had blood samples drawn. Following smoking, subjects rated the cigarette on a variety of sensory dimensions; they also rated smoking satisfaction. Analysis of variance indicated that nicotine played an important sensory role for a variety of dimensions related to cigarette taste and sensory impact but not perceived draw. Principal-components analyses indicated that sensory factors were at least as important as nicotine pharmacology (indirectly indexed by the pre-to post-smoking rise in blood nicotine concentration) when considering smoking's overall effects on satisfaction, product acceptance, and reduction in desire to smoke.

Adult↗
PubMed1996

Effects of cigarette smoking on EEG spectral-band power, dimensional complexity, and nonlinearity during reaction-time task performance.

Electroencephalogram (EEG) and heart rate (HR) were recorded while individuals performed visual and auditory go/no-go reaction time (RT) tasks. Overnight-abstaining smokers smoked two types of cigarettes in a single morning session. The first type was smoked once and had a nicotine yield of 0.05 mg. Two cigarettes of the second type (1.1 mg) were smoked. Four recordings were made: presmoking, postsmoking 0.05 mg, and postsmoking each 1.1 mg. HR was increased only by the first 1.1-mg cigarette. Smoking both the 1.1-mg cigarettes decreased RT. Smoking the first 1.1-mg cigarette increased EEG power in the beta2 band. A flexible effect of smoking the first 1.1-mg cigarette on EEG dimensional complexity (DCx) was obtained at locus Cz. Specifically, DCx was (a) raised when the presmoking level was low, (b) not affected when the presmoking level was intermediate, and (c) lowered when the presmoking level was high. Surrogate-data testing indicated the presence of nonlinearity in the EEG data that was not affected by smoking. Decreased RT was associated with increased DCx in the visual task only.

Adult↗
PubMed1996

Psychophysiological and subjective effects of cigarettes having varying nicotine yields but relatively constant "tar' yields.

Thirty-two subjects were tested in five double-blind sessions-16 subjects in the morning (a.m.) following overnight smoking abstention, and 16 in the afternoon (p.m.) following ad lib smoking. In each session, subjects smoked 1 of 5 cigarettes having the following FTC nicotine/'tar' yields in mg: 0.08/8.5, 0.17/9.1, 0.37/9.8, 0.48/9.8, and 0.74/10.4. On a pre- to postsmoking basis, blood nicotine and heart rate increased with nicotine yield. The effect of nicotine yield on changes in self-rated anxiety was an inverted-U function, but this effect was possibly confounded by baseline differences. The following effects on EEG spectral-band magnitude were also obtained: (1) nicotine yields > or = 0.17 mg decreased delta; (2) nicotine yields of 0.37 and 0.48 mg decreased theta in a.m. subjects; (3) nicotine yields > or = 0.37 mg decreased alpha, the effect being greater in a.m. subjects; (4) no effect of yield on beta 1 was obtained; (5) nicotine yields of 0.48 and 0.74 mg increased the Cz-minus-T5 differential in beta 2. Pre- to postsmoking changes in this measure of beta 2 were not correlated with either blood nicotine or anxiety.

Adolescent↗
PubMed1995

Flow cytometric determination of intracellular calcium changes in human peripheral blood mononuclear cells during conjugation to tumour cell lines.

Using a flow cytometric assay, conjugate formation between human peripheral blood mononuclear cells (PBMC) and three different human tumour cell lines has been analysed. Changes in the intracellular calcium levels of PBMC were monitored using the calcium sensitive dye Fluo-3. Target cell populations were distinguished by forward scatter or following loading with the fluorescent dye, SNARF-1. Intracellular calcium was expressed as a ratio of fluorescence of conjugated to unconjugated PBMC and followed for ten minutes after initiation of conjugation. The results demonstrate an apparent increase in intracellular calcium in PBMC conjugated to the NK-sensitive cell line K562, and that the kinetics and magnitude of this response varied considerably between individuals. Tumour cells which were resistant to lysis (as determined in a 4 h chromium release assay) were also capable of eliciting a calcium response from PBMC. Although the induction of a rise in intracellular calcium was therefore not correlated with cytotoxicity, it was greater in IL-2-activated PBMC upon exposure to the same target cell lines as PBMC.

Aniline Compounds↗
PubMed1995

Comparison of measured and FTC-predicted nicotine uptake in smokers.

Cigarette smokers have a wide variety of "tar" and nicotine yields to choose from in the current market, ranging from 0.5 mg "tar" and less than 0.05 mg nicotine to 27 mg "tar" and 1.8 mg nicotine by the Federal Trade Commission (FTC) method. To understand better the relationship between FTC nicotine yields and actual nicotine uptake in smokers, we have studied nicotine uptake in 33 smokers of self-selected products representing four "tar" groupings: 1 mg "tar" (1MG), ultra-low "tar" (ULT), full-flavor low "tar" (FFLT), and full flavor (FF) cigarettes. These cigarette categories had mean FTC nicotine yields of 0.14, 0.49, 0.67, and 1.13 mg/cigarette, respectively. The subjects smoked their usual brand of cigarette ad libitum and provided a 24-h urine sample for total nicotine uptake analysis over a period during which the number of cigarettes smoked was recorded. Nicotine uptake was determined by monitoring urinary nicotine and its metabolites, including the glucuronide conjugates. Daily nicotine uptake was 9.1 +/- 7.3 mg (range 1-21 mg) for 1MG, 19.2 +/- 10.0 mg (range 4-42 mg) for ULT, 21.8 +/- 9.4 mg (range 13-38 mg) for FFLT, and 37.1 +/- 14.4 mg (range 21-60 mg) for FF smokers. On a per cigarette basis, yields were 0.23 +/- 0.11, 0.56 +/- 0.23, 0.60 +/- 0.18, and 1.19 +/- 0.43 mg nicotine, respectively. Although individual variability was fairly large (CVs of 0.39-0.80), means for the different groups showed that lower FTC yield smokers not only absorb less nicotine per 24-h period, but also per cigarette smoked. These data suggest that nicotine uptake is a function of individual smoking behavior within product design limits. We conclude from these data that, while FTC yield cannot precisely predict nicotine uptake for an individual smoker, it is useful in predicting and comparing actual nicotine uptake by smokers who select cigarettes with a particular FTC yield.

Adult↗
PubMed1995

Caffeine and smoking: subjective, performance, and psychophysiological effects.

The effects of caffeine and smoking on cognitive performance, subjective variables, heart rate, and EEG were assessed in two sessions. In one session, subjects received caffeine (2.5 mg/kg bodyweight), while in the other they received placebo. In both sessions they smoked a cigarette (8 cued puffs) having a nicotine yield of 1.2 mg. Caffeine produced an increase in self-reported muscular tension and tended to increase anxiety and delta magnitude. Smoking facilitated performance of a paper-and-pencil math task and increased heart rate. Smoking also appeared to produce cortical activation as indexed by decreased right frontal delta, decreased right centro-parietal theta, globally increased alpha, and increased centro-occipital/decreased posterior-temporal beta 1. Smoking also increased central/decreased posterior-temporal beta 2. Smoking and caffeine did not interact for any measure, suggesting that the epidemiological link between smoking and coffee drinking may have a non-pharmacological basis.

Adult↗
PubMed1995

Grief responses, coping processes, and social support of widows: research with Roy's model.

This ex post facto descriptive correlational design study of widows during their second year of bereavement utilizes Roy's adaptation model as a guiding framework. Contextual stimuli (social support, social network, income/education, spiritual beliefs) were related to the cognator function (coping process), which was related to adaptation outcome (grief response). Significant moderate positive relationships were found between social support and coping process, and between social network and coping process. A significant relationship was also found between coping process and grief response. The path model accounted for 18% explained variance.

Adaptation, Psychological↗
PubMed1995

A late sternal wound infection caused by hematogenous spread of bacteria.

A 56-year-old man presented with a sternotomy wound infection 6 months after coronary artery bypass grafting. The organism responsible was group B beta-hemolytic Streptococcus. This organism was simultaneously cultured from an infected diabetic ulcer on the patient's foot as well as from a total knee prosthesis. The Streptococcus apparently spread hematogenously to the sternum, an extremely rare cause of sternotomy wound infection.

Bacteremia↗
PubMed1994

Expression and functional characterisation of a synthetic version of the human D4 dopamine receptor in a stable human cell line.

A synthetic version of the human D4 (hD4) dopamine receptor was prepared. The G/C content of the natural gene was reduced by 14% without altering the amino acid composition of the corresponding protein sequence. HEK293 cells were transfected with the synthetic hD4 gene and stable clones resistant to G418 selected. The hD4 receptor expressed from the synthetic gene had identical pharmacological characteristics to the native hD4 receptor [(1991) Nature 350, 610-619; (1992) Nature 358, 149-152]. Functional studies with cells expressing the synthetic hD4 gene indicated negative coupling of this receptor to adenylate cyclase.

Adenylyl Cyclases↗
PubMed1994

Processing of viable group A streptococci leads to major histocompatibility complex class II presentation of T cell epitopes from the major protective antigen.

We have previously mapped major histocompatibility complex (MHC) class II-restricted T cell epitopes of the surface M protein of type 5 group A streptococci (M5) and show here that two out of four epitopes investigated were efficiently processed during incubation of viable streptococci with spleen cells for presentation to M5-specific murine T cell clones. Viable streptococci were processed more efficiently than heat-killed bacteria suggesting that secreted virulence factors of streptococci do not obstruct processing of streptococcal antigens in the dose range used. Epitopes from different regions of M5 could be ranked according to the efficiency with which they were processed, which may contribute to their relative immunodominance. It was further demonstrated that T cell clones specific for M5 308-319, an epitope from the M type conserved carboxy-terminal half of M5, cross-reacted between M5, M6 and M12, but not M49, streptococci. Helper T cell epitopes which are shared between streptococcal M types and are presented by MHC class II molecules on antigen-presenting cells after processing of viable streptococci could be particularly useful in the design of multivalent streptococcal vaccines.

Amino Acid Sequence↗