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Biomedical subjects

J C Craig

Publications and source records attributed to J C Craig.

At least 127 records · Page 7Linked to original sources
PubMed1989

Synthesis and dopaminergic activity of 2-substituted octahydrobenzo[f]quinolines.

A series of 2-substituted octahydrobenzo[f]quinolines has been synthesized and assayed for dopamine agonist activity. Only the compounds corresponding to the beta-rotameric conformation of dopamine showed biphasic activity in competition binding studies with the radioligand [3H]spiroperidol. These findings suggest that the congeners possessing the beta-rotamer conformation show receptor-binding characteristics that resemble those of the ergolines more closely than do those of the corresponding alpha-rotamer congeners.

Animals↗
PubMed1989

Interference in localizing tactile stimuli.

A series of experiments investigated the ability of subjects to localize a tactile stimulus in the presence of an additional, extraneous tactile stimulus. The subject's task was to localize a tactile stimulus (target) presented at one of several locations on his or her left index fingerpad. The target stimulus, generated on a 6 x 24 array of stimulators, was presented either by itself or in the presence of an extraneous stimulus (masker) that either preceded or followed the target. The localizability of the target was affected by the temporal separation between the target and masker in much the same way as previous studies have shown identification of tactile patterns to be affected. Unlike previous identification results, presenting the masking stimulus to the same location as the target interfered with localizability, although not as much as did presenting the masker to a different location. The results are discussed in terms of their implications for identification and discrimination of tactile patterns.

Adult↗
PubMed1989

A comparison of discrimination and identification of vibrotactile patterns.

Both discrimination and identification tasks have been used to assess subjects' abilities to perceive vibratory spatial patterns presented to the skin. The present study examined discrimination and identification performance under comparable conditions. In Experiment 1, subjects attempted to discriminate a pair of patterns on some blocks of trials and to identify both members of a pair on other blocks. For both tasks, the time between the members of the pair was varied. Discrimination performance could be predicted accurately from identification data. Analysis of performance on identification trials indicated that subjects used discriminability information to identify pairs. In Experiment 2, discrimination and identification were compared when the temporal separation between patterns was fixed and a masking stimulus followed each pattern after a variable delay. Results suggest that temporal masking, rather than the time available for processing pattern information, is the major limitation in both discrimination and identification of sequences of tactile patterns.

Adult↗
PubMed1988

T-cell-mediated suppression of Epstein-Barr virus-induced B lymphocyte activation in multiple sclerosis.

Significantly reduced levels of T-cell-mediated "suppression" of numbers of Epstein-Barr virus (EBV)-activated B lymphocytes which secrete IgG or IgM were found in preparations of mononuclear cells (MNC) from peripheral blood of 28 patients with multiple sclerosis (MS) compared with 28 healthy subjects, all seropositive for EBV. A statistically significant correlation was not found between the suppression of EBV-induced activation of B lymphocytes and either EBV-specific T-cell-mediated cytotoxicity or numbers of T8-positive cells.

Antibody Formation↗
PubMed1988

Correlation of alpha- and beta-rotameric forms of 2-substituted octahydrobenzo[f]quinoline dopamine congeners with high and low affinity states of the anterior pituitary dopamine receptor and prolactin inhibition.

The flexible dopamine (DA) molecule exists in one or the other of its two conformational extremes (alpha- or beta-rotamer) and its receptor in the anterior pituitary gland exists in a high and a low affinity state. A series of novel, rigid DA congeners (2-substituted octahydrobenzo[f]quinolines) was synthesized and used to investigate the conformation of DA preferred by its anterior pituitary receptor and the significance of recognition of the two affinity states to the inhibition of prolactin (PRL) secretion. Analysis of competition curves of congeners for [3H]spiperone binding to bovine anterior pituitary membranes was used to calculate affinity constants. Congeners in the beta-rotamer conformation showed a biphasic competition curve as observed for DA. The curves were resolved into high (nM) and low (microM) affinity binding sites. This biphasic binding could be converted to monophasic low affinity binding in the presence of a nonhydrolyzable GTP analog. The congeners in the alpha-rotameric conformation showed monophasic low affinity binding. The potency of congeners to suppress PRL release was evaluated in cell cultures of dispersed bovine anterior pituitary. Congeners recognizing the high affinity binding site were 100-fold more potent in suppressing PRL release than those recognizing only low affinity binding sites. Dihydroxy congeners versus monohydroxy congeners and cyanomethyl group substituted versus methylthiomethyl substituted congeners occupied greater proportions of high affinity binding sites. Increasing proportions of high affinity sites occupied increased the potency of the congener to suppress PRL release. These results suggest that the beta-rotameric conformational extreme of DA is preferred by its receptor in the anterior pituitary gland and that the high affinity state of this receptor is functionally important in mediating the inhibition of PRL secretion.

Binding, Competitive↗
PubMed1987

Breast fluid cholesterol and cholesterol epoxides: relationship to breast cancer risk factors and other characteristics.

We measured levels of cholesterol and its oxidation products, 5,6 alpha- and beta-epoxides and their common hydrolysis product cholestane triol, in breast fluids of women without breast disease, compared these levels to serum cholesterol levels, and explored associations of these breast fluid measurements with known breast cancer risk factors and other characteristics. Subjects were 105 women with no history of breast disease from whom breast fluid could be obtained by nipple aspiration. The four breast fluid measurements were significantly correlated with each other (P less than 0.0001) but none was correlated with serum cholesterol. In subsequent analyses restricted to breast fluid cholesterol and cholesterol beta-epoxide, cholesterol levels (but not beta-epoxide levels) increased with age and were higher in white than nonwhite women. Both measurements were low in women who were lactating, who were parous, or who had breast-fed. The lower levels among parous women persisted for at least 2 years postpartum or postlactation. Because breast fluid levels of cholesterol beta-epoxide are reduced for some time following a birth or cessation of lactation, the alveolar-ductal systems of parous women presumably have less cumulative exposure to this potentially carcinogenic substance. This biochemical mechanism may, in part, explain the observed reduction of breast cancer risk associated with parity.

Adult↗
PubMed1987

Analysis of cholesterol, cholesterol-5,6-epoxides and cholestane-3 beta,5 alpha,6 beta-triol in nipple aspirates of human breast fluid by gas chromatography/mass spectrometry.

A method has been developed for the quantitative determination of cholesterol and three of its major oxidative metabolites (the 5 alpha,6 alpha-epoxide, the 3 beta,5 alpha,6 beta-triol, and the 5 beta,6 beta-epoxide) in a single sample of human breast fluid (2-50 microliters), using gas chromatography/mass spectrometry with selected ion monitoring. High specificity and reliable quantification is achieved by the use of the inverse stable isotope dilution method, employing deuterium-labeled variants of the compounds as internal standards.

Adult↗
PubMed1986

Temporal integration and vibrotactile backward masking.

Subjects were presented with vibrotactile target patterns to their left index fingertips. The target patterns varied in the number of line segments that they contained and were presented in the presence or absence of a backward-masking stimulus. The stimulus onset asynchrony (SOA) between the target and masker was varied. In an identification task, subjects' errors indicated that the effect of the masker at brief SOAs was to increase the perceived number of line segments in the target. This effect diminished with increasing SOA, and at the longest SOAs subjects confused targets with patterns containing the same number of line segments but varying in how the line segments were related. In an estimation task, the effect of the masker was to increase the number of line segments estimated to be contained in the target pattern. The effect of the masker at brief SOAs is discussed in terms of an integration theory of vibrotactile backward masking. At longer SOAs, the results suggest that the masker may interfere with the extraction of relational information in the target pattern.

Adult↗
PubMed1986

Benzene levels in ambient air and breath of smokers and nonsmokers in urban and pristine environments.

Benzene levels in human breath and in ambient air were compared in the urban area of San Francisco (SF) and in a more remote coastal pristine setting of Stinson Beach, Calif. (SB). Benzene analysis was done by gas chromatography-mass spectroscopy (GC-MS). Ambient benzene levels were sevenfold higher in SF (2.6 +/- 1.3 ppb, n = 25) than SB (0.38 +/- 0.39 ppb, n = 21). In SF, benzene in smokers' breath (6.8 +/- 3.0 ppb) was greater than in nonsmokers' breath (2.5 +/- 0.8 ppb) and smokers' ambient air (3.3 +/- 0.8 ppb). In SB the same pattern was observed: benzene in smokers' breath was higher than in nonsmokers' breath and ambient air. Benzene in SF nonsmokers' breath was greater than in SB nonsmokers' breath. Marijuana-only smokers had benzene breath levels between those of smokers and nonsmokers. There was little correlation between benzene in breath and number of cigarettes smoked, or with other benzene exposures such as diet. Of special interest was the finding that benzene in breath of SF nonsmokers (2.5 +/- 0.8 ppb) was greater than that in nonsmokers ambient air (1.4 +/- 0.1 ppb). The same was true in SB, where benzene in nonsmokers breath was greater than ambient air (1.8 +/- 0.2 ppb versus 1.0 +/- 0.1 ppb on d 1 and 1.3 +/- 0.3 ppb versus 0.23 +/- 0.18 ppb on d 2). This suggests an additional source of benzene other than outdoor ambient air.

Adolescent↗
PubMed1985

Determination of chlorpromazine and its major metabolites by gas chromatography/mass spectrometry: application to biological fluids.

A method for the quantitative determination of chlorpromazine and five of its major metabolites in a single sample of biological fluid in the ng/ml range has been developed utilizing gas chromatography/mass spectrometry with selected ion recording. The assay is highly specific and quantification is accomplished by an inverse stable isotope dilution technique, using deuterium-labeled variants of the compounds as internal standards. In this way the concentrations of chlorpromazine and five of its major metabolites (the sulfoxide, the N-oxide, the monodemethylated, the didemethylated, and the 7-hydroxylated compounds) can be determined in biological fluids. Levels in humans have been measured both in plasma and in red blood cells and are compared to those found in related in vitro studies.

Biotransformation↗
PubMed1985

Dual carbon-labeled isotope experiments using D-[6-14C] glucose and L-[1,2,3-13C3] lactate: a new approach for investigating human myocardial metabolism during ischemia.

Simultaneous lactate production and extraction have been previously demonstrated in the myocardium in patients with coronary artery disease. To quantitate this lactate production and determine its source, dual carbon-labeled isotope experiments were performed. L-[1,2,3-13C3] lactate and D-[6-14C] glucose were infused in 10 patients with significant coronary artery disease. Metabolic samples were obtained at rest and during atrial pacing. Despite net chemical myocardial lactate extraction in the 10 patients at rest and no evidence of clinical ischemia, the L-[1,2,3-13C3] lactate analysis demonstrated that lactate was being released by the myocardium. During atrial pacing, seven patients did not develop clinical symptoms of ischemia, and the chemical lactate analysis showed net lactate extraction. However, tracer analysis demonstrated that there was a significant increase in the lactate released during atrial pacing (from 6.9 +/- 2.3 to 16.2 +/- 10.1 mumol/min) (p less than 0.05). In these seven patients, circulating glucose was the source of 23 +/- 15% of the lactate released at rest, and there was no significant change during pacing. The remaining three patients had mild chest pain and net chemical lactate production during pacing. Lactate release detected by the tracer increased from 5.7 +/- 3.0 mumol/min at rest to 50.9 +/- 16.8 mumol/min during pacing (p less than 0.01). In these patients, the contribution of glucose to lactate production increased significantly during pacing-induced clinical ischemia from 25 +/- 22 to 67 +/- 14% (p less than 0.005). Thus, dual carbon-labeled isotopic experiments are powerful tools for investigating myocardial metabolic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

Ipsilateral versus bilateral placement of a tactile vocoder display.

A tactile vocoder was evaluated in a word recognition task. The vocoder consisted of a pair of two-dimensional vibrotactile arrays on which subjects placed their fingers. For one group of subjects, the two arrays contacted two fingers on the same hand (ipsilateral condition); for the second group, the arrays contacted two fingers on opposite hands (bilateral condition). Performance was better in the bilateral condition; however, the rate at which words were acquired, even in the bilateral condition, was less than that reported by Brooks and Frost [J. Acoust. Soc. Am. 74, 34-39 (1983)] with a tactile vocoder placed on the arm.

Communication Devices for People with Disabilities↗
PubMed1985

Tactile pattern perception and its perturbations.

One of the problems encountered in conveying information to the skin by means of vibratory patterns is that presenting patterns, such as letters of the alphabet, in close spatial and temporal proximity, may result in considerable masking. Generally, there is more interference when the masking stimulus follows the target (backward masking) than when it precedes it (forward masking). Masking has also been demonstrated with vibrotactile patterns derived from speech signals. Masking may be reduced by increasing the temporal and spatial separation between patterns; however, other problems may arise when such separations are made. Because stimulus onset asynchrony appears to be the critical temporal dimension for masking, it may prove difficult to reduce masking by increasing the temporal separation between patterns without also reducing the rate at which the patterns are presented. Increasing the spatial separation between patterns may lead to problems in combining the patterns from spatially distinct sites on the skin. This latter difficulty may be due to problems in attending to several sites of stimulation simultaneously.

Attention↗
PubMed1985

Metabolic fate of extracted glucose in normal human myocardium.

Glucose is an important substrate for myocardial metabolism. This study was designed to determine the effect of circulating metabolic substrates on myocardial glucose extraction and to determine the metabolic fate of glucose in normal human myocardium. Coronary sinus and arterial catheters were placed in 23 healthy male volunteers. [6-14C]Glucose was infused as a tracer in 10 subjects. [6-14C]Glucose and [U-13C]lactate were simultaneously infused in the other 13 subjects. Simultaneous blood samples were obtained for chemical analyses of glucose, lactate, and free fatty acids and for the the isotopic analyses of glucose and lactate. Glucose oxidation was assessed by measuring myocardial 14CO2 production. The amount of glucose extracted and oxidized by the myocardium was inversely correlated with the arterial level of free fatty acids (r = -0.71; P less than 0.0001). 20% (range, 0-63%) of the glucose extraction underwent immediate oxidation. Chemical lactate analysis showed a net extraction of 26.0 +/- 16.4%. However, isotopic analysis demonstrated that lactate was being released by the myocardium. In the 13 subjects receiving the dual-carbon-labeled isotopes, the lactate released was 0.09 +/- 0.04 mumol/ml and 49.5 +/- 29.5% of this lactate was from exogenous glucose. This study demonstrates that the circulating level of free fatty acids plays a major role in determining the amount of glucose extracted and oxidized by the normal human myocardium. Only 20.1 +/- 19.4% of the glucose extracted underwent oxidation, and 13.0 +/- 9.0% of the glucose extracted was metabolized to lactate and released by the myocardium. Thus, 60-70% of the glucose extracted by the normal myocardium is probably stored as glycogen in the fasting, resting state.

Adult↗
PubMed1985

Subsets of T lymphocytes in relation to T lymphocyte function in multiple sclerosis.

T lymphocyte control of Epstein-Barr virus (EBV) infection of autologous B lymphocytes was examined in parallel to the enumeration of subpopulations of mononuclear cells in 22 multiple sclerosis (MS) patients and in 22 healthy individuals. All were seropositive for EBV. The incidence of lack of T cell control was significantly higher in patients than in controls, confirming previous published work. In the present study, we have shown in addition a significantly reduced proportion of OKT8+ cells and a significantly increased ratio of OKT4/OKT8 cells in the group of patients with lack of control. The findings point to abnormal immunoregulation in MS.

Adrenocorticotropic Hormone↗