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Biomedical subjects

S C Chan

Publications and source records attributed to S C Chan.

At least 91 records · Page 5Linked to original sources
PubMed1994

Abnormal skin irritancy in atopic dermatitis and in atopy without dermatitis.

BACKGROUND AND DESIGN: Past observations have shown increased irritancy in patients with "conditioned hyperirritability" due to active dermatitis, including atopic dermatitis (AD). In less active atopic conditions, irritancy levels are less certain. We have utilized 48-hour Finn Chamber testing with graded dilutions of sodium lauryl sulfate to detect irritancy thresholds in well-defined groups of patients with AD, inactive AD, and allergic respiratory disease with no dermatitis and in normal nonatopic subjects. RESULTS: Significantly greater frequency of response to sodium lauryl sulfate in both AD groups and also in patients with allergic rhinitis with no dermatitis was seen. Effective concentrations of sodium lauryl sulfate causing irritation in 50% or more of subjects (ED50) ranged from 0.0625% to 0.31% in all atopic groups, percentages that were significantly lower than the normal ED50 of 0.60%. Response intensity was also significantly greater in each atopic group. CONCLUSIONS: Our results showed significantly greater irritant responses in atopic subjects with no skin disease or in subjects with inactive AD and confirmed past findings that showed greatly increased irritancy in patients with active AD. We hypothesize that abnormal intrinsic hyperreactivity in inflammatory cells, rather than in skin cells, in atopic individuals predisposes to a lowered threshold of irritant responsiveness.

Adolescent↗
PubMed1993

Altered prostaglandin E2 regulation of cytokine production in atopic dermatitis.

The monocyte-derived inflammatory mediator, prostaglandin E2 (PGE2), can reduce IFN-gamma production, and this in turn may relate to IL-4 up-regulation of IgE synthesis and impaired delayed hypersensitivity in atopy. These abnormalities may relate to the cyclic nucleotide dysregulation in atopic dermatitis (AD), where monocyte cyclic AMP-phosphodiesterase (PDE) activity is increased and the consequent reduction in cAMP levels allows increased inflammatory responsiveness. In this study, we assessed the relationship between PGE2 and IFN-gamma production along with abnormal PDE activity in AD monocytes. Blood mononuclear leukocytes (MNL) from normal and AD donors were cultured for 24 hours, and supernatants were assayed for PGE2 and IFN-gamma by RIA. Spontaneous PGE2, but not leukotriene C4 release, was significantly increased in AD MNL (p < 0.05), although IFN-gamma levels were reduced (p < 0.05). In contrast, purified AD T cells, after removal of PGE2-producing monocytes, produced levels of IFN-gamma significantly higher than in normal T cell cultures. Inhibition of PGE2 synthesis by indomethacin caused increased IFN-gamma production by MNL cultures. We noted a strong negative correlation (r = 0.77) between PDE activity and IFN-gamma production in MNL cultures. We speculate that abnormal cyclic nucleotide metabolism caused by increased PDE activity may allow elevated levels of PGE2 production by AD monocytes. This study demonstrates a regulatory interaction between monocytes and T cells in AD and suggests that PGE2 may be an extracellular messenger between these cells to modulate IFN-gamma production.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

A multiple sequence comparison method.

This article presents a new method for the comparison of multiple macromolecular sequences. It is based on a hierarchical sequence synthesis procedure that does not require any a priori knowledge of the molecular structure of the sequences or the phylogenetic relations among the sequences. It differs from the existing methods as it has the capability of: (i) generating a statistical-structural model of the sequences through a synthesis process that detects homologous groups of the sequences, and (ii) aligning the sequences while the taxonomic tree of the sequences is being constructed in one single phase. It produces superior results when compared with some existing methods.

Amino Acid Sequence↗
PubMed1993

Immunochemical characterization of the distinct monocyte cyclic AMP-phosphodiesterase from patients with atopic dermatitis.

BACKGROUND: Previous findings have suggested that the immunopathology of patients with atopic dermatitis (AD) results from altered cellular responses caused by cyclic nucleotide regulatory abnormalities. One such defect is the increased degradation of the second messenger, cyclic adenosine monophosphate (cAMP), by elevated cAMP-phosphodiesterase (PDE) activity in patients with AD. METHODS: We used two monoclonal antibodies to identify the major PDE isoform in AD blood monocytes. We have also characterized the abnormal PDE activity by means of chromatofocusing and sucrose gradient centrifugation. RESULTS: The chromatofocusing technique allowed the separation of a PDE-containing fraction (isoelectric point = 6.1) from AD monocytes but not from normal cells. This monocyte fraction accounted for most of the elevated leukocyte-PDE activity and was a cytosolic, cAMP-specific, low Michaelis constant, calcium-calmodulin-dependent enzyme, inhibited by the cAMP-PDE inhibitor, Ro 20-1724. The majority of the PDE activity in this chromatofocused fraction was immunoadsorbed by the solid-phase immobilized antibodies against calcium-calmodulin-dependent PDE. CONCLUSIONS: The increased degradation of cAMP by a unique form of PDE may cause defective regulation of intracellular functions of AD monocytes, leading to the characteristic hyperreactive immune and inflammatory events. Characterization of PDE isoenzymes from different leukocyte subpopulations may allow further expansion of cell-directed therapy for inflammatory disease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Modulation of leukocyte cyclic AMP phosphodiesterase activity by recombinant interferon-gamma: evidence for a differential effect on atopic monocytes.

Mechanisms of interferon-gamma (IFN-gamma) effects on monocytes are poorly defined. Evidence for altered IFN-gamma responses and increased monocyte cyclic AMP phosphodiesterase (PDE) activity in atopic dermatitis (AD) suggested a possible relationship. PDE activity in response to IFN-gamma was assessed in normal and atopic monocytes to evaluate the IFN-gamma regulatory role in cell function. Adherence-isolated peripheral blood monocytes were exposed to recombinant human IFN-gamma at 0.1-300 U/ml in Gey's balanced salt solution for varying time periods. Anti-IFN-gamma was used as control. PDE activity was measured by radioenzyme assay using 1 microM cyclic AMP as final substrate concentration. IFN-gamma caused a dose-dependent increase in PDE activity of normal monocytes and the effect was neutralized by anti-IFN-gamma. By contrast, in atopic monocytes, PDE activity was not affected by IFN-gamma at low dose, while at concentrations greater than 200 U/ml, it significantly reduced phosphodiesterase activity. IFN-gamma of PDE activity may alter normal monocyte functions by decreasing cyclic AMP levels. Paradoxical PDE unresponsiveness probably reflects maximal PDE activation in atopic monocytes. This elevated PDE activity is inhibited by high IFN-gamma levels. Reduction of atopic monocyte PDE activity may help to normalize immune function and could account for recent reports of therapeutic efficacy of IFN-gamma in AD.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Increased interleukin 6 production by T cells derived from patients with atopic dermatitis.

Many immunologic aspects of atopic dermatitis have been studied, but basic pathobiologic mechanisms of this disease remain unknown. In this study, we measured the production of interleukin-6 (IL-6) by peripheral blood T cells and monocytes from patients with atopic dermatitis in comparison to normal control subjects and patients with chronic psoriasis. We found that peripheral blood T cells isolated from patients with atopic dermatitis produced significantly higher levels of IL-6 (36.1 +/- 5.1 units/ml, n = 22) than T cells derived from either normal subjects (12.6 +/- 1.9 units/ml, n = 22) or patients with chronic psoriasis (26.7 +/- 4.1 units/ml, n = 7). T-cell activation was also measured in the patients with atopic dermatitis by soluble serum IL-2 receptor levels and were found to be significantly higher (623.7 +/- 8.1 units/ml, n = 8) than normal subjects (357.2 +/- 26.0 units/ml, n = 8). In contrast to the increased production of IL-6 by T cells in atopic dermatitis, there was no significant difference in the IL-6 production by peripheral blood monocytes derived from patients with atopic dermatitis compared to normal subjects. Thus, peripheral blood T cells derived from patients with AD spontaneously produce increased amounts of IL-6 compared to T cells from normal subjects, which may reflect the increased activation state of T cells in atopic dermatitis. These data support the concept that activated T cells or subsets of T cells may be important effector cells in mediating inflammatory activity in atopic disease.

Biological Availability↗
PubMed1993

Increased interleukin-4 production by atopic mononuclear leukocytes correlates with increased cyclic adenosine monophosphate-phosphodiesterase activity and is reversible by phosphodiesterase inhibition.

Previous studies have shown that leukocytes from patients with atopic dermatitis have increased levels of cyclic adenosine monophosphate (cAMP)-phosphodiesterase activity. This increased activity accounts for subnormal cAMP responses and correlates with increased in vitro immunoglobulin E production. To better understand the mechanism of this effect, we studied the relationship between phosphodiesterase activity and interleukin-4, a T-cell-derived cytokine that is a major regulator of immunoglobulin E production. Cultures stimulated with anti-CD3 or with phorbol myristate acetate plus ionophore significantly increased interleukin-4 production, and levels were consistently highest in cells from atopic subjects. Interleukin-4 production was higher, on a per T-cell basis, in mononuclear leukocyte cultures than in cultures of pure T cells, suggesting the possibility of a monocyte factor acting to increase interleukin-4 production. We next examined the effect of the phosphodiesterase inhibitor Ro 20-1724 on interleukin-4 production and found a significant reduction in cultures of atopic mononuclear leukocytes. This phosphodiesterase inhibitor effect appeared to act primarily on monocytes and correlated with increased intracellular cAMP levels. These studies demonstrate increased interleukin-4 production by atopic T cells. This abnormality can be reversed by inhibition of cAMP-phosphodiesterase, suggesting a possible therapeutic target for control of atopic disease.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1993

Effect of protein quality and evaporative cooling on lactational performance of Holstein cows in hot weather.

Twenty-four Holstein cows in midlactation during summer in southern Arizona were fed diets supplemented with a combination of blood, fish, and soybean meals (high quality protein) or corn gluten meal (low quality protein). Diets were balanced for CP content and estimated ruminal protein degradability, but they differed in Lys concentration (.98 vs. .59% of DM). Milk yield for the 56-d trial was higher by 11% for cows fed high than for cows fed low quality protein and higher by 9% for cows receiving evaporative cooling plus shade than for cows receiving shade alone. Milk fat and protein yields also were greater for high than for low quality protein and for evaporatively cooled plus shade than for shade treatments. Intake of DM tended to be higher for cooled cows but was unaffected by protein source. Cooled cows had lower rectal temperatures (38.6 vs. 39.1 degrees C) and respiration rates (64 vs. 82/min) than noncooled cows. Interactions between protein quality and cooling method were not statistically significant; however, cooled cows fed high quality protein had higher milk yield than noncooled cows. Digestibility of DM was higher for the low than for the high quality diet, but CP digestibilities were not different. Cows fed supplemental protein of higher Lys content were more productive.

Animal Feed↗
PubMed1993

Effect of three supplemental fat sources on lactation and digestion in dairy cows.

Tallow, Ca salts of palm fatty acids, or prilled fatty acids were added at 2.5% to a control diet (3.7% fatty acids) containing 7.2% ammoniated whole cottonseed. Diets were fed to midlactation cows (6 cows per treatment) for 72 d to determine effects of fat supplementation and fat source on lactation performance and nutrient digestibilities. Dry matter intake did not differ among treatments. Milk yield was 31.6 kg/d for the control and increased an average of 2.1 kg/d with fat supplementation. Source of supplemental fat did not significantly affect lactation performance. Added fat decreased milk protein content but did not affect protein yield. Milk fat, lactose, and SNF contents did not differ among treatments. Overall fat supplementation did not affect digestibilities of DM, ADF, or NDF but decreased digestibility of fatty acids. Contribution of de novo fatty acids to milk fat was decreased with fat supplementation. Addition of 2.5% fat to a diet containing a medium amount of fat from whole cottonseed increased milk yield. Tallow, Ca salt of palm fatty acids, and prilled fatty acids did not differ in milk yield response.

Adipose Tissue↗
PubMed1993

Differential inhibitor effects on cyclic adenosine monophosphate-phosphodiesterase isoforms in atopic and normal leukocytes.

Increased cyclic adenosine monophosphate-phosphodiesterase activity in atopic leukocytes correlates with abnormal inflammatory and immune cell function in atopic dermatitis. The increased phosphodiesterase activity may affect many pathways of cell regulation and thus could be an important therapeutic target for management of cutaneous and respiratory inflammation. The increased PDE activities in atopic monocytes and lymphocytes reflect isoforms with increased maximum rate of metabolism but first order rate constant similar to that of the enzyme in normal cells. Both isoforms can be classed into the phosphodiesterase IV group with sensitivity to the inhibitor Ro 20-1724. In this study we used an in vitro assay to assess the effects of various phosphodiesterase inhibitors on enzyme isoforms in mononuclear leukocytes and purified leukocyte subpopulations from patients with atopic dermatitis and normal subjects. The atopic isoenzyme was found to be consistently more sensitive to a number of phosphodiesterase inhibitors. The descending order of potency for mononuclear leukocytes was rolipram, Ro 20-1724, nitraquazone, isobutyl methyl xanthine, and theophylline. Nitraquazone showed greater inhibitory effect on atopic T cells than did Ro 20-1724. Cyclic adenosine monophosphate levels increased in atopic mononuclear leukocytes incubated with Ro 20-1724 but not in normal cells. We also measured inhibitor effects on intact cells and cell homogenates, allowing discrimination of inhibitor capacity to enter intact cells. The differential inhibitor effect on various leukocyte subpopulations was demonstrated by a greater sensitivity of atopic lymphocytes and T cells for nitraquazone than for Ro 20-1724. In contrast, the latter inhibitor was a more potent inhibitor of mononuclear leukocyte and monocyte phosphodiesterase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

A survey of multiple sequence comparison methods.

Multiple sequence comparison refers to the search for similarity in three or more sequences. This article presents a survey of the exhaustive (optimal) and heuristic (possibly sub-optimal) methods developed for the comparison of multiple macromolecular sequences. Emphasis is given to the different approaches of the heuristic methods. Four distance measures derived from information engineering and genetic studies are introduced for the comparison between two alignments of sequences. The use of entropy, which plays a central role in information theory as measures of information, choice and uncertainty, is proposed as a simple measure for the evaluation of the optimality of an alignment in the absence of any a priori knowledge about the structures of the sequences being compared. This article also gives two examples of comparison between alternative alignments of the same set of 5SRNAs as obtained by several different heuristic methods.

Algorithms↗
PubMed1992

Relationship between increased cyclic AMP-phosphodiesterase activity and abnormal adenylyl cyclase regulation in leukocytes from patients with atopic dermatitis.

Atopic dermatitis (AD) is characterized by a variety of abnormal physiologic and pharmacologic responses in the skin. Leukocyte abnormalities of the cyclic nucleotide system include increased cAMP phosphodiesterase (PDE) and adenylyl cyclase activities. We have evaluated the possibility that a defect of the inhibitory GTP-binding protein (Gi) might cause inadequate modulation of adenylyl cyclase activity in AD leukocytes. We carried out a series of studies assessing adenylyl cyclase and Gi subunits in monocyte membranes. Using both pertussis toxin ribosylation and direct monoclonal antibody labeling of Gi proteins, we have shown evidence for a decrease or possible absence of one of the Gi proteins in atopic monocyte membranes. A genetic defect or toxin-mediated abnormality in leukocyte membrane Gi could account for these findings. Increased cAMP degradation by PDE may be a compensatory mechanism for increased cAMP synthesis that is regulated by GTP-binding proteins. But this increased PDE activity also rendered AD leukocytes hypo-responsive to immunofunction regulatory signals mediated by cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Synergistic effects of interleukin 4 and interferon-gamma on monocyte phosphodiesterase activity.

Patients with atopic dermatitis (AD) have elevated leukocyte cyclic AMP-phosphodiesterase (PDE) activity and increased in vitro IgE synthesis compared to normal (NL) subjects. Interleukin 4 (IL-4), interferon-gamma (IFN-gamma), and PDE inhibitor have been shown to regulate in vitro IgE synthesis. This study investigated whether soluble T-cell factors such as IL-4 and IFN-gamma could account for elevated PDE activity in patients with AD. Both rhIL-4 and IFN-gamma significantly increased normal monocyte PDE activity to a maximum of 188% (n = 6, p less than 0.05) and 315% above control (n = 3, p less than 0.05), respectively. At concentrations below 0.1 units/ml IL-4 and IFN-gamma had synergistic effects on activation of monocyte PDE. AD and NL T-cell culture supernatants also significantly stimulated normal monocyte PDE activity, but the stimulatory activity was not significantly greater in the AD T-cell supernatants. The effect of both cytokines and T-cell supernatants on normal monocytes was inhibited by antibodies against IL-4 and IFN-gamma, respectively. This study demonstrates that IL-4 and IFN-gamma can increase PDE activity in normal monocytes. Though the levels of IL-4 and IFN-gamma in T-cell supernatants are undetectable with an enzyme-linked immunosorbent assay (ELISA) assay, the concentration of these cytokines below the detectable level can significantly increase PDE activity of monocytes in a synergistic and dose-dependent manner. These results suggest that cytokine-mediated activation of monocytes can increase PDE activity. Furthermore, lymphokines may play an important role in modulating the cyclic nucleotide regulatory pathway.

Dermatitis, Atopic↗
PubMed1992

The upgraded Finapres 2300e. A clinical evaluation of a continuous noninvasive blood pressure monitor.

Measurements from the upgraded Finapres 2300e continuous noninvasive blood pressure monitor, the Finapres 2300 and Colin oscillometric noninvasive blood pressure monitor were compared with invasive arterial line blood pressure readings. Fifteen young Chinese patients undergoing elective spinal surgery of more than 2 h duration had contemporaneous blood pressure measurements digitally recorded every minute. Data were analysed using methods described by Bland and Altman to assess agreement of noninvasive devices with an arterial line. Results showed that although the Finapres 2300e was significantly more accurate than the Finapres 2300 and Colin noninvasive blood pressure monitors it could not be recommended as a substitute for continuous arterial line blood pressure monitoring. Both Finapres devices demonstrated reductions in accuracy related to time (drift) and over-read diastolic and mean pressures by 5-8 mmHg throughout the range of mean arterial line pressures (bias). The Colin was consistently less accurate than the Finapress monitors and performed worst at low mean arterial line pressures.

Adolescent↗
PubMed1991

Urinary excretion of free toluenediamines in a patient with polyurethane-covered breast implants.

We report the detection of free 2,4-toluenediamine in urine of a patient implanted with polyurethane-covered breast implants. Samples were collected on several dates, ranging from 21 days to seven months after the insertion of the implants, and these samples all showed the presence of free 2,4-toluenediamine at a concentration of about 1 micrograms/L. The chemical was not found in a urine sample collected before implantation. This finding is important for risk assessment of cancer in patients with this type of breast implant because the chemical is a suspected carcinogen. Free 2,6-toluenediamine, an isomer, was also found in all samples from this patient.

Adult↗
PubMed1991

Drug analysis at the 1988 Olympic Winter Games in Calgary.

A comprehensive drug testing program was carried out during the 16 days of the 1988 Olympic Winter Games in Calgary, Canada. State-of-the-art technology was applied, involving high-resolution gas chromatography, high-performance liquid chromatography, gas chromatography/mass spectrometry, fluorescence polarization immunoassay, and radioimmunoassay. Samples from selected athletes were screened for five drug classes: stimulants, narcotic analgesics, anabolic steroids, beta-blockers, and diuretics. In addition, samples were also screened for local anesthetics, corticosteroids, beta-human choriogonadotropin, and cannabinoids. During the 16-day event, 428 urine samples were processed and 3090 screening procedures performed. We describe the methods for analysis at the Olympic Games and present the results.

Adrenergic beta-Antagonists↗