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Biomedical subjects

K Gilliland

Publications and source records attributed to K Gilliland.

At least 19 recordsLinked to original sources

Immunolocalization of 5alpha-reductase isozymes in acne lesions and normal skin.

BACKGROUND: Dihydrotestosterone mediates androgen-dependent diseases, such as acne, hirsutism, and androgenetic alopecia. This hormone is produced from testosterone by the 5alpha-reductase enzyme. There are 2 isozymes of 5alpha-reductase (types 1 and 2) that differ in their localization within the body and even within the skin. Activity of the type 1 isozyme predominates in sebaceous glands, where it may be involved in regulation of sebum production. Since specific inhibition of 5alpha-reductase type 1 may represent a novel therapeutic approach to acne, it is important to define the localization of these isozymes in normal sebaceous follicles and acne lesions. OBSERVATIONS: Skin biopsy specimens were obtained from the backs of 11 subjects: 8 with acne and 3 without acne. Sections of normal follicles, open comedones, closed comedones, and inflammatory lesions were incubated with antibodies to types 1 and 2 5alpha-reductase. In all samples, the type 1 antibody localized specifically to sebaceous glands, and the type 2 antibody localized to the companion layer of the hair follicle (the innermost layer of the outer root sheath) and granular layer of the epidermis. Localization of the type 2 isozyme was also noted within the walls of open and closed comedones and in endothelial cells from sections of inflammatory lesions. CONCLUSIONS: The immunolocalization of 5alpha-reductase isozymes in normal sebaceous follicles and acne follicles is similar to the pattern described in terminal hair follicles and corresponds with the findings of biochemical studies that have demonstrated predominance of type 1 activity in sebaceous glands. The function of type 2 5alpha-reductase in comedones or endothelial cells in inflammatory lesions is unknown.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

The melanocortin 5 receptor is expressed in human sebaceous glands and rat preputial cells.

Melanocortins regulate pigmentation, adrenal hormone secretion, immune functions, lipid metabolism, and feeding behaviors in rodents. These peptides include adrenocorticotrophic hormone, melanocyte stimulating hormone, beta-lipotrophin, and the endorphins. Lipid metabolism in sebaceous glands and preputial glands of rodents is regulated by alpha-melanocyte stimulating hormone, the major agonist for melanocortin receptors. Five melanocortin receptor subtypes have been identified that differ in their tissue localization and affinities for melanocortin ligands. Targeted disruption of the melanocortin 5 receptor in transgenic mice results in widespread dysfunction of exocrine glands, including a marked decrease in sebum production. A role for melanocortins in the modulation of human sebum production has not been established. The goal of this study is to determine which melanocortin receptors are expressed in human sebaceous glands. Messenger RNA was isolated from human sebaceous glands and the reverse transcriptase polymerase chain reaction was performed using primers specific for each of the melanocortin receptor subtypes. Transcripts were detected for the melanocortin 5 receptor. A polyclonal chicken antihuman antibody to the melanocortin 5 receptor localized to sebaceous glands, eccrine glands, hair follicles, and epidermis in human skin, rat skin, cultured human sebocytes, and rat preputial cells. Presence of the melanocortin 5 receptor protein in human sebaceous glands and rat preputial glands was further verified by Western blotting. These data support further investigation of the role of melanocortins in the regulation of human sebum production and support the use of the rat preputial system as an experimental model in sebaceous gland physiology.

Animals↗

Androgen metabolism in sebaceous glands from subjects with and without acne.

OBJECTIVE: To determine if there are differences in the activity of 17beta-hydroxysteroid dehydrogenase and 5alpha-reductase (responsible for the production of testosterone and dihydrotestosterone, respectively) in sebaceous glands obtained from men and women with and without acne. DESIGN: Single-center examination of androgen levels and sebaceous gland enzyme activity in a cohort of volunteers. SETTING: Academic referral center. PATIENTS: Thirty-four subjects, consisting of 8 women with acne, 10 women without acne, 8 men with acne, and 8 men without acne. INTERVENTIONS: Single visit for blood sampling and 2 biopsies of forehead skin. MAIN OUTCOME MEASURES: Serum levels of androgens were determined and compared with the activity of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase in sebaceous glands microdissected from skin samples. RESULTS: No significant differences in the activity of 5alpha-reductase or 17beta-hydroxysteroid dehydrogenase in sebaceous glands according to the presence of acne were noted in either men or women. The activity of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase was significantly greater in sebaceous glands from men (n = 16) than women (n = 17). The oxidative activity of 17beta-hydroxysteroid dehydrogenase was 2-fold higher in men than women. Serum levels of dehydroepiandrosterone sulfate, androstenedione, testosterone, and dihydrotestosterone were significantly higher in women with acne than in women without acne. No differences in serum androgen levels were noted in men on the basis of the presence of acne. CONCLUSIONS: Higher serum androgen levels are associated with the presence of acne in women. A role for locally produced androgens in this process, however, cannot be excluded.

17-Hydroxysteroid Dehydrogenases↗

Assessing the laryngeal cough reflex and the risk of developing pneumonia after stroke.

OBJECTIVE: To determine the effectiveness of a new reflex cough test, using nebulized tartaric acid, in the evaluation of the laryngeal cough reflex and the development of aspiration pneumonia. STUDY DESIGN: In this two-phase study, the cough test assessed the cough reflex in 161 stroke subjects. Phase 1 was a double-blinded prospective study of 40 subjects scheduled to have both modified barium swallow and the reflex cough test. Phase 1 subjects with an abnormal cough test showed an increased pneumonia incidence, and therefore, phase 2 was not blinded. In phase 2, 121 subjects were evaluated using the cough test; 38 received a modified barium swallow. Test results were compared using the Fisher exact test. RESULTS: A total of 131 subjects from both phases had a normal reflex cough test; none developed pneumonia (p < .01). Thirty subjects from both phases had abnormal reflex cough test results; 5 developed pneumonia. Modified barium swallow findings did not reliably indicate the risk for developing pneumonia. Specificity of a normal reflex cough test was 100%. CONCLUSION: The reflex cough test reliably evaluated the laryngeal cough reflex and the associated risk of developing aspiration pneumonia in stroke patients. Testing the laryngeal cough reflex may significantly reduce morbidity, mortality, and costs in stroke patients.

Aged↗

Oxidative activity of the type 2 isozyme of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) predominates in human sebaceous glands.

Sebum production is regulated by the opposing effects of androgens and estrogens. The intracrine activity of steroid metabolizing enzymes is important in regulating sebum production because these enzymes can convert weak steroids from the serum into potent androgens and estrogens within the sebaceous gland (SG). 17Beta-hydroxysteroid dehydrogenase (17beta-HSD) interconverts weak and potent sex steroids via redox reactions. In this regard, it may function as a gatekeeping enzyme regulating the hormonal milieu of the SG. Six isozymes of 17beta-HSD have been identified that differ in their substrate preference and their preference to produce weak or potent sex steroids via oxidation or reduction, respectively. The goals of this study are: (i) to identify which isozyme (s) of 17beta-HSD is active in SG; (ii) to determine if its activity differs in facial skin compared with nonacne-prone skin that may account for the regional differences in sebum production; (iii) to compare the activity of 17beta-HSD in intact glands and in SG homogenates; and (iv) to determine if 13-cis retinoic acid inhibits 17beta-HSD activity. Human SG were assayed for 17beta-HSD activity using estrogens, androgens, and progestins as substrates. Oxidative activity of the type 2 isozyme predominated in all samples tested. Although transcripts for the types 1, 2, 3, and 4 isozymes were detected using reverse transcriptase-polymerase chain reaction, only mRNA for the predominant type 2 isozyme and the type 4 isozyme were detected in northern analysis. Greater reductive activity of 17beta-HSD was noted in SG from facial areas compared with nonacne-prone areas, suggesting an increased net production of potent androgens in facial areas. Oxidation was more predominant over reduction in intact SG compared with homogenized SG, thus supporting the hypothesis that 17beta-HSD protects against the effects of potent androgens in vivo. Activity of the type 2 17beta-HSD was not inhibited by 13-cis retinoic acid. In conclusion, SG possess the cellular machinery needed to transcribe the genes for the type 1-4 isozymes of 17beta-HSD. At the protein level, however, oxidative activity of the type 2 isozyme predominates, suggesting that 17beta-HSD isozyme activity may be translationally regulated.

17-Hydroxysteroid Dehydrogenases↗

Activity of 5-alpha-reductase and 17-beta-hydroxysteroid dehydrogenase in the infrainfundibulum of subjects with and without acne vulgaris.

Linoleic acid deficiency, interleukin 1, retinoids and androgens have been implicated as causative factors in the follicular hyperkeratinization seen in acne. The goal of this study was to test the hypothesis that more androgens are produced in follicles of acne subjects compared to subjects without acne. Thirty-four subjects (males and females with and without acne) were studied. The activity of 5 alpha-reductase (5 alpha-R) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was determined in keratinocytes cultured from the infrainfundibulum and epidermis. Mean enzyme activities were slightly higher in the acne groups compared to the groups without acne, but differences were not statistically significant, perhaps due to limitations of this in vitro model. The activity of both 5 alpha-R and 17 beta-HSD was significantly greater in infrainfundibular keratinocytes compared to epidermal keratinocytes in all subject groups. 17 beta-HSD activity was 2.5- to 7-fold greater than the activity of 5 alpha-R in infrainfundibular keratinocytes. The regulation of 17 beta-HSD by endogenous factors may be important in determining the directional activity of 17 beta-HSD and hence the local concentration of testosterone within the infrainfundibulum. Additional studies of the effects of androgens on follicular keratinization are needed.

17-Hydroxysteroid Dehydrogenases↗

Activity of type 1 5 alpha-reductase is greater in the follicular infrainfundibulum compared with the epidermis.

The enzyme 5 alpha-reductase converts testosterone (T) to dihydrotestosterone (DHT). Although this enzyme has been localized to various regions of the pilosebaceous unit, its activity has not been studied in the follicular portion of either vellus or sebaceous follicles. The goal of our study was to determine the relative activities of 5 alpha-reductase within various regions of these follicles with particular emphasis on the infrainfundibulum. A finding of increased 5 alpha-reductase activity in upper follicles compared to epidermis might support the hypothesis that increased follicular production of DHT is involved in the hyperkeratinization observed in this region of the follicle in acne vulgaris. 5 alpha-reductase activity was determined at pH 5 (optimal for the type 2 isozyme) and pH 7 (optimal for the type 1 isozyme) in isolated infrainfundibular segments from sebaceous and vellus follicles, homogenized epidermis from various anatomical areas and in microdissected segments of the pilosebaceous unit from breast skin of normal subjects. Enzyme activity was also determined at pH 7 in cultured infrainfundibular keratinocytes and in interfollicular epidermal keratinocytes. Homogenates of infrainfundibular segments demonstrated significantly greater activity at pH 7 compared to pH 5 (P < 0.001), confirming activity of the type 1 5 alpha-reductase in this region. Activity of 5 alpha-reductase was much lower in homogenized epidermis and did not demonstrate a clear pH preference. Keratinocytes cultured from the infrainfundibulum demonstrated significantly greater 5 alpha-reductase activity compared to keratinocytes from interfollicular epidermis (P = 0.04). In the dissected segments of pilosebaceous units from breast skin, 5 alpha-reductase activity was greatest in the sebaceous gland followed by the sebaceous duct, infrainfundibulum, whole skin and epidermis. These data indicate that 5 alpha-reductase activity varies within regions of the pilosebaceous unit and compared with interfollicular epidermal cells, infrainfundibular keratinocytes have an increased capacity for producing androgens which may play a role in the follicular hyperkeratinization seen in acne.

Adolescent↗

Activity of the type 1 5 alpha-reductase exhibits regional differences in isolated sebaceous glands and whole skin.

The presence of 5 alpha-reductase (5 alpha-R) in skin may indicate that the androgen regulation of sebaceous glands and sebum production requires the local conversion of testosterone to dihydrotestosterone. The goals of this study were to identify which isozyme of 5 alpha-R (type 1 or type 2) is expressed in sebaceous glands from facial areas, scalp, and non-acne-prone areas; to determine if 5 alpha-R activity is concentrated in sebaceous glands; to assess whether there are regional differences in this enzyme's activity; and to test the effects of azasteroid inhibitors and 13-cis retinoic acid on 5 alpha-R in these tissues. Sebaceous glands were microdissected from facial skin, scalp, and non-acne-prone skin (arm, breast, abdomen, leg), and the activity of 5 alpha-R was determined. A total of 49 samples from 23 male and 21 female subjects without acne (age range, 16 to 81 years, 56 +/- 20 years [mean +/- SD]) was analyzed. The biochemical properties of the enzyme in each of the samples tested are consistent with those of the type 1 5 alpha-R. Minimal to no type 2 5 alpha-R was detected. The level of 5 alpha-R activity was significantly higher in the sebaceous glands compared to whole skin in facial skin (p = 0.047), scalp (p = 0.039), and non-acne-prone skin (p = 0.04). Enzyme activity in sebaceous glands from facial skin and scalp was significantly higher than in a comparable amount of sebaceous gland material obtained from non-acne-prone areas (32 +/- 6 [mean +/- SEM]), 35 +/- 7 (mean +/- SEM) versus 6.0 +/- 3.0 (mean +/- SEM) pmol/min/mg protein, p = 0.014 and 0.007, respectively). Finasteride and 13-cis retinoic acid were poor inhibitors of the enzyme with 50% inhibitory concentration values greater than 500 nM. These data demonstrate that in the skin from older patients without acne the type 1 isozyme of 5 alpha-R predominates, its activity is concentrated in sebaceous glands and is significantly higher in sebaceous glands from the face and scalp compared to non-acne-prone areas, and the action of 13-cis retinoic acid in the control of acne is not at the level of 5 alpha-R. Furthermore, we suggest that specific inhibition of the type 1 5 alpha-R may offer a viable approach to the management of sebum production and, hence, acne.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Eysenck's arousal theory of introversion-extraversion: a converging measures investigation.

Convergent electroencephalographic, performance, and psychometric measures of arousal were used to test predictions based on H. J. Eysenck's (1967) theory. Twelve introverts and 12 extraverts had their brainstem auditory evoked responses (BAERs) monitored under 3 levels of caffeine administration (0.0, 1.5, and 3.0 mg/kg) and 3 levels of task demand (resting, simple response time, and complex response time). Results revealed a decrease in the latency of Wave V of the BAER as a function of personality, with introverts evidencing significantly shorter latency of Wave V as compared with extraverts. Faster conduction time between Waves I-III and I-V were also found in introverts. Caffeine at either the 1.5 or 3.0 mg/kg level was associated with decreased latency of Wave V, compared with the placebo condition. No personality differences in subjective arousal or reaction time performance were found across any of the conditions.

Adolescent↗

Specialty nursing council: a peer support group for nurses in independent roles.

As nurses move into more nontraditional, expanded roles, they sometimes lack a social and professional support group within the work setting. Feeling isolated and lacking support, several clinical nurse specialists (CNSs) at a large county institution began the Specialty Nursing Council. The Specialty Nursing Council provides a means of networking and support for nurses in specialty roles in a three institution health care campus. Monthly meetings are conducted to bring members together and for continuing education programs. The keys to success in forming this type of council are: 1) a dedicated group that plans, organizes, and distributes informational material; 2) common goals and objectives; 3) direct benefits to members.

Humans↗

Epidural abscesses of the spine: case comparisons.

Epidural abscesses of the spine generally arise from staphylococcal infections that by hematologic spread or direct invasion affect the integrity of the vertebral column or meningeal coverings of the spinal cord. A case comparison approach highlights goal-oriented nursing interventions which assist the patient in the adaptation to and recovery from this unique central nervous system infection.

Abscess↗

Compliance, low literacy, and locus of control.

Compliance remains a critical, complex issue in health care today. As outlined, many interrelated factors affect levels of compliance and noncompliance. Assessing literacy and locus of control may assist the health care professional in identifying persons less likely to comply with medical treatments. Although compliance remains difficult to predict, these components should be considered carefully in patient-professional relationships and patient education.

Attitude to Health↗

Ad lib caffeine consumption, symptoms of caffeinism, and academic performance.

The authors explored the relationship between ad lib caffeine consumption in college students and the incidence of caffeinism, characterized by heightened anxiety, depression, and various psychophysiological reactions. Students were randomly selected from four groups (abstainers from caffeine and low, moderate, and high consumers). A survey battery assessed the effects of caffeine, incidence of psychophysiological disorders, state-trait anxiety, and depression. The moderate and high consumer groups combined reported significantly higher trait anxiety and depression scores when compared with abstainers. The high consumer group also reported significantly higher levels of symptoms of caffeinism, higher frequency of psychophysiological disorders, and lower academic performance.

Age Factors↗

Individual differences in diurnal rhythms and multiple activation states: a reply to M. W. Eysenck and Folkard.

Three issues raised by M. W. Eysenck and Folkard are discussed. These include (a) just what individual difference variable is mediating the time of day and caffeine effects; (b) what the difference is in the diurnal rhythms of low and high impulsives; and (c) whether it is necessary to postulate multiple activation states. Suggestions for future research are then given.

Arousal↗

The interactive effect of personality, time of day, and caffeine: a test of the arousal model.

The personality dimension of introversion/extraversion is one of the few personality dimensions that can be reliably identified from study to study and investigator to investigator. The importance of this demension within personality theory is due both to the stability of the trait and the influential theory of H. J. Eysenck. The basic assumption in Eysenck's theory of introversion/extraversion is that the personality differences between introverts and extraverts reflect some basic difference in the resting level of cortical arousal or activation. Assuming that there is a curvilinear relationship (an inverted U) between levels of stress and performance leads to a test of this arousal theory. That is, moderate increases in stress should hinder the performance of introverts who are presumably already highly aroused. However, the same moderate increase in stress might help the performance of the presumably underaroused extraverts. Revelle, Amaral, and Turriff reported that the administration of moderate doses of caffeine hindered the performance of introverts and helped the performance of extraverts on a cognitive task similar to the verbal test of the Graduate Record Examination. Assuming that caffeine increases arousal, this interaction between introversion/extraversion and drug condition supports Eysenck's theory. This interaction was explored in a series of experiments designed to replicate, extend, and test the generality of the original finding. The interaction between personality and drug condition was replicated and extended to additional cognitive performance tasks. However, these interactions were affected by time of day and stage of practice, and the subscales of introversion/extraversion, impulsivity, and sociability, were differentially affected. In the morning of the first day, low impulsives were hindered and high impulsives helped by caffeine. This pattern reversed in the evening of the first day, and it reversed again in the evening of Day 2. We concluded that the results from the first day of testing require a revision of Eysenck's theory. Instead of a stable difference in arousal between low and high impulsives, it appeared that these groups differed in the phase of their diurnal arousal rhythms. The result is that low impulsives are more aroused in the morning and less aroused in the evening than are the high impulsives. A variety of peripheral or strategic explanations (differences in caffeine consumption, guessing strategies, distraction, etc.) for the observed performance increments and decrements were proposed and tentatively rejected. It seems probable that some fundamental change in the efficiency with which information is processes is responsible for these performance changes.

Arousal↗

Binocular summation and peripheral visual response time.

Six males were administered a peripheral visual response time test to the onset of brief, small stimuli imaged in 10 degrees arc separation intervals across the dark adapted horizontal retinal meridian under binocular and both monocular viewing conditions. This was done in an attempt to verify the existence of peripheral binocular summation using a response time measure. The results indicated that from 50 degrees arc right to 50 degrees arc left of the line of sight binocular summation is a reasonable explanation for the significantly faster binocular data. The stimulus position by viewing eye interaction was also significant. A discussion of these and other analyses is presented along with a review of related literature.

Adolescent↗

Tartaric acid-induced cough and the superior laryngeal nerve evoked potential.

The purpose of this study was to stimulate the laryngeal cough reflex using a nebulized, mild chemical irritant and to record an associated laryngeal evoked potential from the internal branch of the superior laryngeal nerve. The laryngeal evoked potential was obtained on ten normal subjects from the right internal branch of the superior laryngeal nerve. The electrodiagnostic setup included an active electrode placed just below the hyoid bone with a 4-cm separation and distal reference. A ground electrode was placed between the active and reference electrodes. The receptors and internal branch of the superior laryngeal nerve were stimulated by inhalation of a nebulized 20% solution of tartaric acid and normal saline. The time line was triggered by a pneumatic switch on initial inspiration of the nebulized tartaric acid. The electrodiagnostic settings were set at a sweep speed of 1 ms/division, a gain of 10 to 20 microV/division, and 20 to 2,000 filters. There were 132 variables recorded from the internal branch of the superior laryngeal nerve of the ten subjects. The mean peak distal latency was 1.66+/-0.42 ms with a 1.6 median, 1.6 mode, and 0.17 variance. The duration was 0.41 ms, and amplitude was 5.19+/-2.91 microV. In conclusion, the laryngeal evoked potential, the afferent component of the involuntary cough reflex, can be recorded from the internal branch of the superior laryngeal nerve after inhalation of tartaric acid-induced cough.

Administration, Inhalation↗