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Biomedical subjects

S C Chan

Publications and source records attributed to S C Chan.

At least 19 recordsLinked to original sources

Overexpression of IL-10 in atopic dermatitis. Contrasting cytokine patterns with delayed-type hypersensitivity reactions.

The skin lesions of patients with atopic dermatitis provide a model to study immunoregulation in human allergy. To determine the local cytokine pattern of cells present (both endogenous and recruited) at the site of disease, we extracted RNA from skin biopsy specimens from patients with atopic dermatitis, allergic contract dermatitis, and positive tuberculin reactions and used PCR to assay for cytokine mRNA. cDNAs were normalized to the intensity of the CD3 delta PCR product as a marker of T cell mRNA. We found overexpression of IL-10 mRNA in atopic dermatitis lesions, in comparison with allergic contact dermatitis lesions and tuberculin reactions. In contrast, IL-4 mRNA was most strongly expressed in allergic contact dermatitis lesions and IFN-gamma mRNA was the predominant cytokine in tuberculin reactions. Using an anti-IL-10 mAb with immunoperoxidase, we localized IL-10 protein to large mononuclear cells in the dermal infiltrate of atopic lesions. After immunomagnetic sorting of mononuclear cell populations from PBMC of atopic dermatitis subjects, IL-10 mRNA as measured by PCR was found to be strongly expressed in CD14+ cells. Spontaneous release of IL-10 from PBMC-derived adherent cells was greater in atopic dermatitis donors than normal controls. We therefore renormalized skin biopsy cDNA according to the level of beta-actin PCR product, as a marker of total cellular mRNA, and found by PCR that IL-10 was nevertheless greatest in atopic dermatitis subjects. We conclude that the relative overexpression of IL-10 in atopic dermatitis greatest in atopic dermatitis subjects. We conclude that the relative overexpression of IL-10 in atopic dermatitis may contribute to the up-regulation of humoral responses and the down-regulation of Th1 responses.

Adult

Monocyte phosphodiesterase abnormalities and dysregulation of lymphocyte function in atopic dermatitis.

The immunologic aberrations associated with atopic dermatitis include the paradox of reduced cell-mediated immune responses in the setting of increased cell-mediated immunity features that resemble allergic contact dermatitis. In this review, we present evidence that abnormalities in monocytes and Langerhans cells alter the function of T-helper-cell subpopulations to cause the immunologic defects associated with atopic dermatitis. Increased monocyte prostaglandin E2 production inhibits Th1 responses, accentuating interleukin (IL)-4 secretion by Th2 cells. Elevated prostaglandin E2 secretion correlates with abnormally increased cyclic adenosine monophosphate-phosphodiesterase activity in monocytes and this, along with other defective inflammatory cell responses, can be normalized in vitro by phosphodiesterase inhibitors. It appears that in addition to prostaglandin E2, IL-10 acts to regulate the balance between Th1 and Th2 functional responses accounting for many atopic features, including increased IL-4, IL-5, and IL-6 production by T cells; increased IgE synthesis; decreased interferon-gamma production; and impaired cell-mediated immune responses. All of these abnormalities can be related to increased phosphodiesterase activity in atopic monocytes, and inhibition of this key enzyme appears to reverse atopic dermatitis inflammatory abnormalities in vitro and in vivo.

Animals

Giant retroperitoneal hemangiopericytoma.

Hemangiopericytomas are rare vascular tumours that are derived from pericytes. Retroperitoneal hemangiopericytomas are usually bulky but clinically silent when diagnosed because of their slow rate of growth. A 49-year-old man, who presented with only vague symptoms of abdominal fullness for several months, was found on computed tomography to have a huge well-defined mass with areas of low attenuation and well-enhanced septa. The tumour was successfully resected and was confirmed to be a malignant retroperitoneal hemangiopericytoma. It measured 30 cm in the greatest dimension. We are prompted to present this case as it is believed to be the largest tumour reported to date.

Hemangiopericytoma

The effect of the geometry of the tibia on prediction of the cruciate ligament forces: a theoretical analysis.

This paper attempts to highlight the importance of the tibial geometry in the prediction of forces along the cruciate ligaments. A two-dimensional model of the knee which comprises the femur, the tibia and the cruciates was used. The model was subjected to an external antero-posterior force and an external axial compressive force. The analysis showed that, with a flat tibial plateau, the tension arising along either cruciate as a result of the application of an external antero-posterior force is determined solely by the inclination of the ligament to the direction of that force; it is independent of the magnitude of the external axial compressive force. A curved tibial plateau modifies the tension along either cruciate, and in the absence of an axial compressive load on the joint small changes in the geometry of the tibial surface cause slight changes (increase/decrease) in the tension. However, these changes can become considerable when a large axial compressive load is applied on the joint. A concave tibial plateau, where the tangent to the surfaces at the point of contact is inclined to the direction of the same external antero-posterior force by 7.8 degrees, can reduce the tension along either cruciate to zero, if a sufficiently large axial compressive load is applied on the joint. It was shown that the convexity of the lateral tibial plateau can provide an important protective function for the posterior cruciate ligament (PCL) at extreme positions of flexion. The analysis showed that the PCL should experience a larger force than that experienced by the anterior cruciate ligament (ACL) and hence explain why the former should be the stronger of the two. Finally, a hypothesis is proposed suggesting that bone remodelling may occur in the tibiae of the older people, causing them to become more concave with age and as a consequence provides greater protection to the cruciates in the aged, in order to compensate for decreasing strength in the older person.

Age Factors

Effect of substituting steam-flaked sorghum for concentrate on lactation and digestion in dairy cows.

Thirty-five lactating cows (110 DIM), allotted to five dietary treatments for 70 d, were fed 0, 15, 30, or 45% of dietary DM as steam-flaked sorghum grain (360 g/L) in place of equal amounts of a mixture (DM basis) of 40% steam-rolled corn, 13% rolled barley, 20% wheat mill run, and 27% ground beet pulp in four diets. Thinly flaked sorghum grain (283 g/L) was also fed at 15% of dietary DM. The DMI tended to increase as flaked sorghum increased. Yields of milk and milk protein and percentages of milk protein and SNF increased linearly as sorghum increased. Milk yield of cows fed 15% of DM as the thinly flaked sorghum was higher than for cows fed the 360 g/L flake at 15% and similar to that of cows fed the 360 g/L flake at 30 or 45%. Feed efficiencies and changes in BW and body condition score were unaffected by treatment. As steam-flaked sorghum increased, digestibilities of DM, OM, ADF, NDF, and CP tended to decrease, except for the thinly flaked sorghum fed at 15% of DM. Apparent starch digestibility in the total tract was unaltered by diet. The 30 to 45% of DM fed as steam-flaked sorghum grain (360 g/L) increased yields of milk and milk protein, and thinly flaked sorghum (283 g/L) fed at 15% of DM increased milk yields over that of the control diet or that with the 360 g/L flake at 15% of DM.

Animal Feed

Influence of steam-flaked sorghum grain and supplemental fat on performance of dairy cows in early lactation.

Effects of sorghum grain processing and fat supplementation on milk yield and composition and nutrient digestibilities were studied. Thirty-six Holstein cows were assigned at 5 d of lactation for 91 d to treatment: 1) dry-rolled sorghum, no added fat; 2) dry-rolled sorghum plus Ca salts of long-chain fatty acids; 3) steam-flaked sorghum, no added fat; and 4) steam-flaked sorghum plus Ca salts of long-chain fatty acids. Fat increased ether extract in diets from 5.7 to 7.5% of DM. Milk yield was 4.0 kg/d (12%) higher for cows fed steam-flaked than dry-rolled sorghum. Fat tended to decrease milk yield because of lower DMI, and feed efficiencies increased 15%. Milk protein decreased .14% on dry-rolled sorghum with added fat, but only .01% on the steam-flaked diet. Milk protein yield was higher for cows fed flaked than rolled sorghum. Flaking decreased milk fat percentage, but not yield. Added fat decreased shorter chain fatty acids in milk (C4 to C14), but oleic acid increased. Flaking increased C10, C12, and C14, but decreased oleic acid. Digestibilities for DM, CP, starch, and ether extract were higher for flaked and fat-supplemented diets. Flanking of sorghum prevented the milk protein decrease reported for early lactation cows fed added fat.

Animal Feed

Formation and identification of carcinogenic heterocyclic aromatic amines in boiled pork juice.

Bacterial frameshift mutagens have been found in boiled pork juice. The mutagenic compounds of boiled pork juice were purified and analyzed by HPLC. The mutagenic fractions corresponding to the peaks of the standard mutagens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) were confirmed by comparison of UV and mass spectra. One gram equivalent of original lean ground pork was estimated to contain 4.1 ng of MeIQx, 3.7 ng of IQ, and 1.2 ng of MeIQ, which accounted for 21.0%, 30.4%, and 38.1%, respectively, of the total mutagenicity. The remaining mutagenic fractions might be diMeIQx isomers. This will be further confirmed by mass spectrometry in future studies. The amount of IQ-type mutagens in boiled pork juice was about 4-fold higher than in broiled beef. Furthermore, we investigated the effects of 20 amino acids, three monosaccharides, and creatinine on mutagen formation when added to the pork juice to elucidate possible precursors leading to the formation of mutagens. Results showed that five amino acids (glutamine, tyrosine, glycine, alanine, and threonine) and two monosaccharides (ribose and glucose) might participate in mutagen formation in boiled pork juice.

Amines

Neonatal leukocyte cAMP-phosphodiesterase determination is not suitable for allergy prediction.

The atopy-predictive value of cord blood (CB) cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) in mononuclear leukocytes (MN) was studied prospectively in 57 neonates. Reliable determination of cAMP-PDE was achieved in only 20 CB samples. The levels tended to be higher in infants developing signs of atopy up to 18 months of age. The combination of CB cAMP-PDE and family history (FH) of allergy showed a higher predictive value (P = 0.040) than each of them separately (P = 0.370 and P = 0.102, respectively). The cAMP-PDE levels in CB also correlated to FH of allergy/atopy in accordance with earlier studies (P = 0.027). In conclusion, determination of cAMP-PDE in neonates may have some predictive value, but it is not suitable for general screening.

3',5'-Cyclic-AMP Phosphodiesterases

Effect of steam flaking of corn and sorghum grains on performance of lactating cows.

The objective of this study was to compare the relative feeding value of sorghum versus corn grain in rolled or steam-flaked forms in diets for lactating dairy cows. Twenty-four Holstein cows (averaging 110 DIM) were divided into four groups and fed diets of 40% grain as dry-rolled sorghum, steam-rolled corn, steam-flaked sorghum, or steam-flaked corn for 70 d. Compared with rolling, flaking of both grains increased yields of milk, milk protein and fat, and protein percentage of milk, but differences tended to be greater for sorghum than for corn. Efficiency of feed utilization was higher for steam-flaked than for dry-rolled sorghum but was unaffected by corn processing. Flaking of both grains increased total tract digestibilities of DM, OM, CP, starch, ADF, and NDF. Estimates for NEL were 21% higher for flaked than for rolled sorghum and 6% higher for flaked than for rolled corn. No differences in performance of cows existed between corn and sorghum grains. Cows fed 40% of their diet as steam-flaked sorghum or corn yielded more milk and milk protein than those fed the rolled form of the grains, and no differences existed between types of grain fed.

Animal Feed

Effect of source and amount of supplemental fat on lactation and digestion in cows.

Thirty Holstein cows averaging 50 DIM were assigned to five dietary treatments for 75 d to determine the effects of source and amount of supplemental fat on milk yield, milk composition, and nutrient digestibilities. Diets were 1) control, 2) diet 1 plus 12% whole cotton-seed, 3) diet 2 plus 2.2% safflower oil, 4) diet 2 plus 2.2% prilled tallow fatty acids, and 5) diet 2 plus 4.4% prilled tallow fatty acids. Milk yield was increased an average of 2.1 kg/d by addition of 2.2% prilled tallow fatty acids or safflower oil to the diet (7% fatty acids) containing 12% whole cottonseed. However, when fatty acids were increased to 9.1% with additional prilled tallow fatty acids, milk yield, DMI, and fatty acid digestibility decreased. Whole cottonseed alone and in combination with all fat additions decreased milk protein concentrations. Safflower oil increased C18:0, C18:1, and C18:2 fatty acids in milk. Digestibilities of OM, NDF, and ADF were not affected by diet. Supplementation of a saturated or unsaturated fat source to increase fatty acid content to 7.0% of dietary DM increased milk yield, but a further increase in fat to 9.1% with the saturated source appeared excessive for cows yielding 30 to 35 kg/d of milk.

Animals

Heat stress interactions with protein, supplemental fat, and fungal cultures.

Cows that were subjected to hot environmental temperatures yielded less milk (3.1 kg/d) on a diet high in CP (18.4%) and of medium degradability (65%) than on diets high in CP of low degradability (59%) or medium in CP (16.1%). The high CP diets were associated with decreased DMI and higher water intake, ruminal NH4, and blood urea. Negative effects on yield from the high CP, medium degradability diet were not observed at moderate temperatures. Evaporative cooling of cows in hot weather resulted in a greater milk yield response to low versus medium rumen-undegradabale protein diets than for uncooled cows. Evaporative cooling of cows also affected response to protein quality. For cooled cows, high Lys diet (soybean, fish, and blood meals) increased milk yield 14% over that with low Lys diet (corn gluten meal), but, for uncooled cows, a high Lys diet only increased yield by 9%. Percentage of CP, degradability, and protein quality had no effect on body temperatures or respiration rates of lactating cows. Some, but not other, reports showed that supplementation of 2 to 2.5% fat to diets fed under hot summer conditions resulted in less yield response than when fat was added at moderate temperatures. In several studies, fungal cultures (3 to 5 g/d) in the diet decreased body temperatures and respiration rates in hot, but not cool, weather. Increased milk yields and cellulose digestibility also resulted from dietary fungal cultures in some, but not all, trials. The mechanism of action exerted by fungal cultures on body temperature and respiration rate is unclear.

Animal Feed

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

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

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

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

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