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Biomedical subjects

J C Stevens

Publications and source records attributed to J C Stevens.

At least 55 records · Page 3Linked to original sources
PubMed1996

Spatial acuity of touch: ubiquitous decline with aging revealed by repeated threshold testing.

Spatial acuity of touch, like that of vision, tends to decline eventually in nearly everybody's lifetime. This has been revealed by more thorough than customary testing of individual young and elderly subjects. Three kinds of acuity threshold were assessed repeatedly in the index finger. These measured ability to discriminate tactile (1) gaps (by a refined version of two-point threshold), (2) orientation of lines (across vs. along the finger), and (3) length of lines. These acuities relate to prominent discriminatory features of braille, and have been shown earlier to average about 1% larger per annum over the adult life span from about 20 to 80 years. Although there were reliable differences among the elderly subjects in the present experiment, all of them tested consistently worse than the least acute young adult controls. The customary single brief threshold tests heretofore applied are inadequate to capture this ubiquitous but differential individual deficit in advanced age; however, the average of six 15- to 20-min tests spread over 3 days proved more than adequate. The method of repeated threshold testing--applied earlier to olfactory and gustatory sensitivity, and now to tactile acuity--serves to dispel the notion that incidence of sensory loss with aging is highly idiosyncratic.

Adult↗
PubMed1996

Spatial acuity of the body surface over the life span.

Spatial acuity over 13 regions of the body was assessed cross-sectionally in 122 male and female subjects between 8 and 87 years of age. Of two measures, the primary one was a threshold for detecting a gap between two points (a refinement of the conventional two-point threshold). The secondary one was a threshold of point localization in 7 of these 13 body regions. The two measures yielded similar pictures of body acuity and age-related changes in acuity, and they agreed in essentials with an early acuity map dating back to Weber in 1835, as cited and confirmed experimentally by Weinstein (1968). To this acuity map, the present study added the dimension of age. The main finding was that aging is much harder on some body regions than on others. Declining acuity with age was found to characterize all regions to one degree or another, but the hands and feet turned out to be far more vulnerable than the more central regions, including the very acute lip and tongue. Deterioration of acuity in the great toe (averaging 400% between youth and advanced age) and fingertip (averaging 130%) may adversely affect such diverse activities as braille reading, grasping, and maintaining balance. The acuity map determined by gap discrimination was essentially the same for males and females; however, males gave significantly smaller localization thresholds than females. In two body regions tested (fingertip and upper lip), children significantly outperformed young adults at gap discrimination.

Adolescent↗
PubMed1996

Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin.

In vitro methods were used to identify the cytochrome P450 (CYP) enzyme(s) involved in S-mephenytoin N-demethylation. S-Mephenytoin (200 microM) was incubated with human liver microsomes, and nirvanol formation was quantitated by reversed-phase HPLC. S-Mephenytoin N-demethylase activity in a panel of human liver microsomes ranged 35-fold from 9 to 319 pmol/min/mg protein and correlated strongly with microsomal CYP2B6 activity (r = 0.91). Additional correlations were found with microsomal CYP2A6 and CYP3A4 activity (r = 0.88 and 0.74, respectively). Microsomes prepared from human beta-lymphoblastoid cells transformed with individual P450 cDNAs were assayed for S-mephenytoin N-demethylase activity. Of 11 P450 isoforms (P450s 1A1, 1A2, 2A6, 2B6, 2E1, 2D6, 2C8, 2C9, 2C19, 3A4, and 3A5) tested, only CYP2B6 catalyzed the N-demethylation of S-mephenytoin with an apparent K(m) of 564 microM. Experiments with P450 form-selective chemical inhibitors, competitive substrates, and anti-P450 antibodies were also performed. Troleandomycin, a mechanism-based CYP3A selective inhibitor, and coumarin, a substrate for CYP2A6 and therefore a potential competitive inhibitor, failed to inhibit human liver microsomal S-mephenytoin N-demethylation. In contrast, orphenadrine, an inhibitor of CYP2B forms, produced a 51 +/- 4% decrease in S-mephenytoin N-demethylase activity in human liver microsomes and a 45% decrease in recombinant microsomes expressing CYP2B6. Also, both CYP2B6-marker 7-ethoxytrifluoromethylcoumarin O-deethylase and S-mephenytoin N-demethylase activities were inhibited by approximately 65% by 5 mg anti-CYP2B1 IgG/mg microsomal protein. Finally, polyclonal antibody inhibitory to CYP3A1 failed to inhibit S-mephenytoin N-demethylase activity. Taken together, these studies indicate that the N-demethylation of S-mephenytoin by human liver microsomes is catalyzed primarily by CYP2B6.

Antibodies, Monoclonal↗
PubMed1995

Life-span development of odor identification, learning, and olfactory sensitivity.

In the first of three studies, children (aged 8 to 14 years) were found to perform worse than young and middle-aged adults in unprompted identification of doors, with average performance much like that of elderly adults. Comparisons on other tasks, specifically odor threshold, prompted odor identification, and object naming (Boston Naming Test), across the life span (five groups) revealed that children have the same excellent olfactory sensitivity as young adults and merely lack odor-specific knowledge that accumulates slowly through life. Such knowledge apparently accumulates so slowly that age-associated discriminative losses, measurable by early middle age, begin to wear away gains obtained through experience before odors can become overlearned. In the second study, a novel adaptive psychophysical method, the step procedure, confirmed the equivalent sensitivity of children and young adults. In the third study, a paired-associate task illustrated the sluggish course of odor learning. Young adults outperformed children, though the youngest group, first graders, made up ground relatively fast. For children and adults, common odors facilitated performance relative to novel odors. The outcome highlighted the relevance of semantic factors in odor learning irrespective of age.

Adolescent↗
PubMed1995

Taste sensitivity and aging: high incidence of decline revealed by repeated threshold measures.

Contrary to what has often been said about the subject, decline in taste sensitivity with aging characterizes virtually everybody and is not the artificial result of averaging large losses of a minority with negligible losses of a majority. This assertion is supported by six repeated measures of sucrose thresholds in each of 15 older (over 64 years) and 15 younger (under 27 years) adult subjects. Threshold was determined by a procedure similar to past studies and with the same results: much scatter and considerable overlap between the thresholds of younger and older subjects. A quite contrasting picture emerges, however, when each subject's six threshold determinations are averaged. Averaging shrinks the individual differences among subjects, as well as the over-lap between younger and older subjects. Although virtually all elderly subjects now revealed taste weakness, reliable individual differences in degree of weakness abound among them, suggesting various individual rates of physiological aging. In contrast, young persons exhibit greater uniformity of sensitivity. These findings were brought out by inter-test correlations, which were much higher for the older subjects; i.e. an older subject who tended to score high (low) on one test tended to score high (low) on the other tests. The study confirms the tenuous nature of brief threshold tests as indices of personal sensitivity as found earlier also in olfactory thresholds and in concurrent measurement of two-point touch thresholds in the present study. This revealed correlated losses between repeated taste and touch thresholds from the same 15 older subjects, unrelated to their exact chronological age.

Adult↗
PubMed1995

Colonic strictures in children with cystic fibrosis.

PURPOSE: To determine the radiographic, clinical, surgical, and histologic findings in children with cystic fibrosis who develop strictures of the colon. MATERIALS AND METHODS: Ten children (five boys, five girls; age range, 2.5-9.0 years; mean age, 5.5 years), who were treated at the practices of the authors, were retrospectively identified and their medical records reviewed. RESULTS: Radiographic manifestations of the colonic disease included mucosal irregularity and spiculation with nodular thickening of the colonic wall and loss of normal colonic haustration. Luminal narrowing involved long segments of the colon. Longitudinal shortening of the colon was also a prominent feature. The decrease in caliber of the bowel ranged from mild narrowing to complete occlusion of the lumen. Histologic examination revealed severe submucosal fibrosis and fatty infiltration with transmural extension of the fibrosis to involve the serosa in some cases. Unlike in Crohn disease, however, acute inflammatory changes were minimal or absent. CONCLUSION: Colonic stricture in children with cystic fibrosis is due to irreversible and frequently progressive narrowing of the colonic lumen.

Child↗
PubMed1995

Dimensions of spatial acuity in the touch sense: changes over the life span.

Spatial acuity of the touch sense and its variation in aging came under psychophysical scrutiny at the fingertip and control body sites. Acuity is viewed as encompassing the discrimination of four features of simple stimulus configurations: (11) discontinuity (gaps in lines or disks), (2) locus on the skin, (3) length (or area), and (4) orientation (e.g., along or across the finger). Each of these dimensions of acuity serves uniquely in tactile perception, as illustrated in the structure of braille. For their measurement, psychophysical tests were developed and refined. These were aimed at freedom from bias, rapid estimation of acuity thresholds in hundreds of subjects, and eventual applicability to the whole body surface. Some 14 versions of the tests were administered in three experiments, yielding 1478 individual thresholds. Experiment I (15 young and 15 elderly subjects) and Experiment II (131 subjects, ages 18 to 87 years) shed light on the nature of discrimination of discontiniuty and orientation. These mainly concern pitfalls of measurement and influence of exact stimulus configuration. Experiment III (115 subjects, ages 8 to 86 years) examined refined versions of tests for all four dimensions of acuity. Four principal findings emerged: (1) At all ages, thresholds for the four dimensions of acuity differ from one another in size--in order from smallest to largest: length, locus, orientation, and discontinuity. Exact sizes differ for transverse and longitudinal stimulus alignment. (2) All four acuity dimensions deteriorate with age, to a first approximation manifesting a constant increase in threshold of approximately 1% per annum between ages 20 and 80 years. That similar rates of deterioration characterize all four dimensions in the fingertip suggests a common mechanism, possibly thinning of the same mediating receptor network. (3) Acuity at more central sites (forearm, lip) deteriorates more slowly than at the fingertip. (4) Individual differences in acuity abound, even after the effects of aging are discounted.

Adolescent↗
PubMed1995

Detection of heteroquality taste mixtures.

Detection thresholds were measured for sweet (sucrose), salty (sodium chloride), sour (citric acid), and bitter (quinine hydrochloride) and for the 11 possible mixtures of these four substances. These 11 mixtures (6 binary, 4 ternary, and 1 quaternary) all turned out to be stimulus additive, in the sense that a person could reliably detect mixtures whose individual components are weaker than their unmixed thresholds. Tastants too weak to be perceived alone can thus make impact when in mixtures. The threshold concentration for a given compound was reduced in approximate proportion to the number of compounds added to it. This liberal heteroquality additivity contests the widespread belief that heteroquality mixtures (different chemicals evoking different qualities) are non-additive and homoquality mixtures (different chemicals evoking the same quality) are additive. Heteroquality additivity emerges on appropriate definition of the subject's task by forced choice (unavailable to earlier investigators), in order to skirt methodological pitfalls. Operating together, homo- and heteroquality additivity may concomitantly enable a person to sense natural mixtures of hosts of weak constituents, such as drinking water. In this regard, gustatory mixtures may function much as do mixtures of frequencies in audition and mixtures of gaseous compounds in olfaction.

Adolescent↗
PubMed1994

Successful treatment response of granuloma annulare and carpal tunnel syndrome to chlorambucil.

We describe a 62-year-old woman in whom skin biopsies verified the clinical diagnosis of granuloma annulare and neurologic and electromyographic studies confirmed the neurologic diagnosis of carpal tunnel syndrome. Short-term treatment with a low dose of chlorambucil taken orally was prescribed. Within weeks, the granuloma annulare had disappeared, and the clinical symptoms of carpal tunnel syndrome had resolved. Electromyography showed variable improvement at the end of treatment and resolution at 9-month follow-up. Our case confirms that short-term treatment of granuloma annulare and associated carpal tunnel syndrome with low-dose chlorambucil is successful.

Carpal Tunnel Syndrome↗
PubMed1994

Vibrotactile and electrotactile perception of time-varying pulse trains.

To establish the best strategy for transmitting speech-derived information via a single tactile channel, measurements were made on the perception of frequency- and/or amplitude-modulated pulse-train stimuli, with a comparison of the electrotactile and vibrotactile modalities. In one experiment, vibrotactile perception of 2-oct step changes in stimulus frequency was found to be significantly better than electrotactile on a time-scale appropriate for the transmission of speech features (e.g., with practiced subjects, information transfer of 69% with 200-ms vibrotactile stimuli, 32% with 200-ms electrotactile stimuli). Perception of step changes in stimulus amplitude was similar in the two modalities when changes in amplitude were tailored to match the different dynamic ranges available. In a second experiment, vibrotactile-perception of voice fundamental frequency with various codings was investigated. Both experiments showed information transfer for vibrotactile stimuli to be greater when frequency and amplitude modulation were used together rather than with one or the other in isolation (sentence-stress identification scores: 66% for FM stimuli, 69% for AM stimuli, 80% for FM/AM stimuli). It is concluded that frequency- and amplitude-modulated vibratory stimulation is a good choice in a practical device for the profoundly hearing impaired.

Adolescent↗
PubMed1993

Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4'-hydroxylation.

In an effort to identify and characterize minor forms of human liver cytochrome P450, immunoblot analyses of microsome samples were developed with antibodies to various P450s that recognized multiple human P450s. Four P450s were recognized in immunoblot analyses of human liver microsome samples developed with an antibody previously demonstrated to specifically recognize rat 2B1/2. Three of these P450s were identified as 2A6, 2C9/10, and 2E1 and the fourth was termed P450UK. A monoclonal antibody to 2C9/10 recognized P450UK in addition to 2C9/10. In order to identify P450UK, it was purified and subjected to amino-terminal amino acid analysis. The amino-terminal sequence obtained for P450UK was identical to the sequence deduced from a cDNA encoding CYP2C19, thus identifying P450UK as 2C19. The relative levels of 2C19 were determined in 14 human liver microsome samples by quantitative immunoblot analyses developed with the anti-2C9/10 antibody. These analyses demonstrated that 2C19 was not detected in one sample and its levels varied 10.5-fold in the remaining samples. The levels of 2C19 were compared to the relative levels and catalytic activities of multiple human liver P450s. The levels of 2C19 and the ability of the samples to 4'-hydroxylate S-mephenytoin were found to strongly correlate (r2 = 0.79). In summary, this is the first demonstration of the expression of 2C19 at the enzyme level, and the correlation studies suggest that 2C19 plays a role in the 4'-hydroxylation of S-mephenytoin.

Amino Acid Sequence↗
PubMed1993

Changes in taste and flavor in aging.

This study aims at understanding the role of mixtures (mutual quality suppression) in the evaluation of impact of the human aging process on the perception of taste. Heretofore, the effect of aging on taste has been directed at threshold and suprathreshold magnitudes of single chemicals (e.g., NaCl, sucrose, citric acid) in aqueous solution. Although absolute thresholds typically rise in advanced age (2 to 9 times, depending on the study), suprathreshold magnitude assessed by magnitude matching seems (except for bitter) to resist change in the way presbycusis spares suprathreshold loudness, fostering the impression that aging may handicap the aged little in the perception of food. Asked, however, to discriminate the presence-absence of the prescribed salt flavoring (nominally suprathreshold) in tomato soup, the young outperformed the middle-aged who, in turn, outperformed the elderly. Moreover, NaCl thresholds in the presence of tomato measured several times higher than in water, but the difference between the young and the elderly continued to hold. Elevation of threshold to much higher levels by mixture suppression leaves the young-elderly difference unchanged, implying that the elderly may fail to detect salt levels that really count in their diet. To examine the relation between age and taste mixtures, we measured detection thresholds: (1) for NaCl in citric acid, from zero to strong; (2) for sucrose in citric acid, from zero to strong; and (3) for citric acid in sucrose, from zero to strong. Whether in water alone or in a weak or strong suppressor, the elderly subjects' threshold was consistently 2 or 3 times higher than that of the young. Moreover, the way in which threshold for one quality rises with concentration of a suppressor is the same, except for constant upward displacement of the elderly peoples' threshold. In general, both young and elderly confuse salty and sour (show large suppression at all concentrations of the suppressor) much more than they confuse sweet and sour (seen mainly at high concentrations of the suppressor). Study of other mixtures is planned.

Adult↗
PubMed1993

Seronegativity for type 1 antineuronal nuclear antibodies ('anti-Hu') in subacute sensory neuronopathy patients without cancer.

We followed 21 patients with sensory neuronopathy without evidence of cancer for up to 23 years. All were seronegative for type 1 antineuronal nuclear antibodies (ANNA-1, also called "anti-Hu"). We additionally studied 67 seropositive patients with sensory neuropathy or a related neurologic syndrome. Ninety-one percent of the seropositive patients had a small-cell lung carcinoma. One, with a normal chest x-ray, had been followed for 7 years for sensory neuronopathy of indeterminate cause before serologic testing for ANNA-1 led to the discovery of the tumor by CT. We conclude that ANNA-1 seropositivity in a patient with sensory neuronopathy is strong evidence for an underlying small-cell lung cancer.

Acute Disease↗
PubMed1993

Variability of olfactory threshold and its role in assessment of aging.

Olfactory thresholds of elderly persons (over 65 years) average one to two orders of magnitude higher than those of young adults (under 30 years). Past studies reveal enormous spreads (typically about three orders of magnitude) of individual thresholds within each age group and extensive overlap between the two groups--enough to question how typically decline in sensitivity characterizes the individual aged person. The present study shows that much of the observed overlap is misleading, because the brief threshold tests usually administered tend to exaggerate individual differences. A more representative assessment of an individual's threshold (for 1-butanol) was achieved by averaging the thresholds from two to eight separate short tests, spread over 4 days. The spread of each group's thresholds (12 young and 12 elderly subjects) narrowed strikingly as the number of tests averaged increased from one to four; further tests accomplished no additional narrowing of spread. Based on a single test, thresholds of young and elderly overlapped in the usual way; but based on four or more tests, thresholds of young and elderly overlapped little or not at all. The outcome (1) argues that decline in smell sensitivity seems to be, after all, a common feature of aging, and (2) sheds light on the sources of variability of sensory thresholds.

Adult↗
PubMed1993

Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450.

(R)- and (S)-fluoxetine were found to be competitive inhibitors of P450 2D6-mediated bufuralol 1'-hydroxylation in vitro, yielding Ki values of 1.38 +/- 0.48 and 0.22 +/- 0.11 microM, respectively. Their N-demethylated metabolites were also found to be potent inhibitors (Ki, (R)-norfluoxetine, 1.48 +/- 0.27 microM; (S)-norfluoxetine, 0.31 +/- 0.04 microM). The microsomal (R)- and (S)-fluoxetine N-demethylase activities for 14 human liver samples were on average 29.6 +/- 13.5 and 19.4 +/- 11.8 pmol of product/min/mg of protein, respectively. The individual rates of N-demethylation correlated with microsomal immunodetectable P450 2D6 levels; (R)-fluoxetine, r = 0.64, P < .05; (S)-fluoxetine, r = 0.63, P < .05. However, this correlation was significantly weaker than the excellent correlation obtained for P450 2D6-marker bufuralol 1'-hydroxylase activity and P450 2D6 levels (r = 0.92, P < or = .01). Quinidine, a potent inhibitor of P450 2D6, inhibited the demethylation of each enantiomer by only approximately 20% at a concentration 300 times greater than the Ki determined for the quinidine inhibition of bufuralol 1'-hydroxylase. Furthermore, antiserum recognizing P450 2D6 inhibited 82% of microsomal bufuralol 1'-hydroxylase activity but only 27% of the (R)-fluoxetine N-demethylase activity in the same human liver sample. In summary, these data indicate that the enantiomers of fluoxetine and norfluoxetine are potent inhibitors of P450 2D6 and that P450 forms other than P450 2D6 appear to be responsible for the majority of microsomal fluoxetine N-demethylation.

Animals↗