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Biomedical subjects

C Tang

Publications and source records attributed to C Tang.

At least 145 records · Page 8Linked to original sources
PubMed1996

Emergence of preferred structures in a simple model of protein folding.

Protein structures in nature often exhibit a high degree of regularity (for example, secondary structure and tertiary symmetries) that is absent from random compact conformations. With the use of a simple lattice model of protein folding, it was demonstrated that structural regularities are related to high "designability" and evolutionary stability. The designability of each compact structure is measured by the number of sequences that can design the structure-that is, sequences that possess the structure as their nondegenerate ground state. Compact structures differ markedly in terms of their designability; highly designable structures emerge with a number of associated sequences much larger than the average. These highly designable structures possess "proteinlike" secondary structure and even tertiary symmetries. In addition, they are thermodynamically more stable than other structures. These results suggest that protein structures are selected in nature because they are readily designed and stable against mutations, and that such a selection simultaneously leads to thermodynamic stability.

Amino Acid Sequence↗
PubMed1996

Flk-1 as a target for tumor growth inhibition.

A number of growth factor receptor tyrosine kinases have been implicated in angiogenesis, including epidermal growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, Flk-1/KDR, Flt-1, Tie-1, and Tek/Tie-2. Flk-1/KDR, a receptor for vascular endothelial growth factor (VEGF), is expressed exclusively in endothelial cells. Using dominant-negative methods, Flk-1 was shown to play a role in angiogenesis and the growth of a variety of tumor types. Because of this, a drug discovery effort was established to identify Flk-1 kinase inhibitors. For initial screening, an ELISA in, a 96-well format was used to measure VEGF-induced Flk-1 tyrosine phosphorylation in whole cells. Compounds that inhibited ligand-induced receptor autophosphorylation were confirmed by antiphosphotyrosine immunoblotting. Inhibition of VEGF-stimulated DNA synthesis in human endothelial cells was also assessed. Inhibitors were further evaluated for their effects on vessel formation using the chorioallantoic membrane assay. Using these methods, antiangiogenesis compounds that inhibit Flk-1 tyrosine kinase activity, endothelial cell mitogenesis, and blood vessel formation in the chorioallantoic membrane assay have been found.

3T3 Cells↗
PubMed1996

Amygdala activity at encoding correlated with long-term, free recall of emotional information.

Positron emission tomography of cerebral glucose metabolism in adult human subjects was used to investigate amygdaloid complex (AC) activity associated with the storage of long-term memory for emotionally arousing events. Subjects viewed two videos (one in each of two separate positron emission tomography sessions, separated by 3-7 days) consisting either of 12 emotionally arousing film clips ("E" film session) or of 12 relatively emotionally neutral film clips ("N" film session), and rated their emotional reaction to each film clip immediately after viewing it. Three weeks after the second session, memory for the videos was assessed in a free recall test. As expected, the subjects' average emotional reaction to the E films was higher than that for the N films. In addition, the subjects recalled significantly more E films than N films. Glucose metabolic rate of the right AC while viewing the E films was highly correlated with the number of E films recalled. AC activity was not significantly correlated with the number of N films recalled. The findings support the view derived from both animal and human investigations that the AC is selectively involved with the formation of enhanced long-term memory associated with emotionally arousing events.

Adult↗
PubMed1996

Characterization of the interface between gamma and epsilon subunits of Escherichia coli F1-ATPase.

The interaction faces of the gamma and epsilon subunits in the Escherichia coli F1-ATPase have been explored by a combination of cross-linking and chemical modification experiments using several mutant epsilon subunits as follows: epsilonS10C, epsilonH38C, epsilonT43C, epsilonS65C, epsilonS108C, and epsilonM138C, along with a mutant of the gamma subunit, gammaT106C. The replacement of Ser-10 by a Cys or Met-138 by a Cys reduced the inhibition of ECF1 by the epsilon subunit, while the mutation S65C increased this inhibitory effect. Modification of the Cys at position 10 with N-ethylmaleimide or fluoroscein maleimide further reduced the binding affinity of, and the maximal inhibition by, the epsilon subunit. Similar chemical modification of the Cys at position 43 of the epsilon subunit (in the mutant epsilonT43C) and a Cys at position 106 of the gamma subunit (gammaT106C) also affected the inhibition of ECF1 by the epsilon subunit. The various epsilon subunit mutants were reacted with TFPAM3, and the site(s) of cross-linking within the ECF1 complex was determined. Previous studies have shown cross-linking from the Cys at positions 10 and 38 with the gamma subunit and from a Cys at position 108 to an alpha subunit (Aggeler, R., Chicas-Cruz, K., Cai, S. X., Keana, J. F. W., and Capaldi, R. A. (1992) Biochemistry 31, 2956-2961; Aggeler, R., Weinreich, F., and Capaldi, R. A. (1995) Biochim. Biophys. Acta 1230, 62-68). Here, cross-linking was found from a Cys at position 43 to the gamma subunit and from the Cys at position 138 to a beta subunit. The site of cross-linking from Cys-10 of epsilon to the gamma subunit was localized by peptide mapping to a region of the gamma subunit between residues 222 and 242. Cross-linking from a Cys at position 38 and at position 43 was with the C-terminal part of the gamma subunit, between residues 202 and 286. ECF1 treated with trypsin at pH 7.0 still binds purified epsilon subunit, while enzyme treated with the protease at pH 8.0 does not. This identifies sites around residue 70 and/or between 202 and 212 of the gamma subunit as involved in epsilon subunit binding.

Amino Acid Sequence↗
PubMed1996

The significance of heregulin in breast cancer tumor progression and drug resistance.

The erbB-2 receptor plays an important role in the prognosis of breast cancer and is expressed at high levels in nearly 30% of tumors in breast cancer patients. While evidence accumulates to support the relationship between erbB-2 overexpression and poor overall survival in human breast cancer, understanding of the biological consequence(s) of erbB-2 overexpression remains elusive. The discovery of heregulin has allowed us to identify a number of related but distinct biological endpoints which appear responsive to signal transduction through the erbB-2/4 receptor. These endpoints of growth, invasiveness, and differentiation have clear implications for the emergence, maintenance, and/or control of malignancy, and represent established endpoints in the assessment of malignant progression in human breast cancer. Preliminary studies in vitro have shown that heregulin induces a biphasic growth effect on cells with erbB-2 overexpression. Interestingly, we observed that expression of heregulin correlates with a more aggressive/invasive, vimentin-positive phenotype in breast cancer cells lines. Therefore, we have postulated that heregulin is involved in breast cancer tumor progression. We have shown that heregulin induces in vitro chemoinvasion and chemotaxis of breast cancer cells as well as growth in an anchorage dependent and independent manner. Interestingly, a heregulin neutralizing antibody inhibits chemotaxis and results in cell growth inhibition and blockade of the invasive phenotype. Strikingly, genetically engineered cells which constitutively express heregulin demonstrate critical phenotypic changes that are associated with a more aggressive phenotype. Specifically, these cells are no longer dependent on estrogen for growth and are resistant to tamoxifen in vitro and in vivo, and moreover these cells metastasize to lymph nodes in athymic nude mice. These tumors appear to have lost bcl-2 expression as compared with the control tumors. In addition, presumably by activation/regulation of topoisomerase II, the heregulin-transfected cells become exquisitely sensitive to doxorubicin and VP-16. Clearly, mechanistic aspects of the erbB-2/4 and heregulin interaction need to be understood from a therapeutic standpoint which could provide additional insights into synergistic treatments for certain patients, or improve treatment regimens for a large number of women. The study of heregulin and its co-expression with erbB-2/4 receptor and the assessment of its involvement in the progression from the in situ stage of breast tumors to the invasive one will additionally increase the relevance of heregulin as a prognostic/diagnostic factor. We believe that our studies provide new insights into breast cancer diagnosis, prognosis, and treatment.

Breast Neoplasms↗
PubMed1996

Changes in substance P in the jejuna of rats after burns.

Radioimmunoassay (RIA) was used to determine the dynamic changes of immunoreactive substance P (iSP) in the jejuna of rats (TBSA 30 per cent full skin thickness burn) during the first 72 h postburn. Immunohistochemistry and image analysis techniques were used to observe and quantitate the SP immunoreactivity (SP-IR) of positive nerve fibres in the villi of jejuna postburn. Changes in the amount of iSP in jejuna of burned rats were: (1) iSP increased significantly at 1 h postburn, and the high level of iSP lasted 4 h; it then decreased greatly 8 h later with the low level of iSP persisting for 72 h. (2) Significant changes in SP-IR-positive nerve fibres in the villi after burn were shown by the immunohistochemical studies including the morphoses; the distributive densities and SP-IR-positive products in the SP-IR-positive nerve fibres. The results quantified by image analysis showed similar alterations in the distributive densities and SP-IR-positive products in the nerve fibres in the villi during 72 h postburn; which were distinctly elevated by 1 hr then dropped by 8 h and 12 h and finally elevated again. The results indicated that the irritation-release and consumption of SP occurred in jejuna of rats after burns. It might be that SP contributed to the postburn intestinal lesion in rats by bioactivities, such as enhancing the vascular permeability and regulating the intestinal movement. The SP peptidergic nerve fibres of the villus had a direct effect on the damage to mucosal epithelia.

Animals↗
PubMed1996

Cerebral metabolic activity correlates of subsyndromes in chronic schizophrenia.

Seventy-nine patients with schizophrenia and 47 healthy controls received positron-emission tomography (PET) with 18F-2-deoxyglucose uptake while executing the Continuous Performance Test (CPT). Patients had been off all psychoactive medication for at least four weeks. Patients' symptoms were assessed with the Brief Psychiatric Rating Scale and factor scale scores were obtained. These scores were used in cluster analysis to identify patients with predominantly delusional, negative, disorganized, and remitted symptoms. To address the interconnective nature of cerebral functioning, regions of interest were defined on the basis of the results of a factor analysis of metabolic rate in selected brain regions. This procedure identified six cortical and eight subcortical region of interest factors. Metabolic rate factor scale scores were compared between the patients' clusters and the healthy controls. The delusional cluster showed a significantly reduced hippocampal activity, while the negative symptoms cluster presented with a prominent hypofrontality and significantly increased left temporal cortex values. Concurrently, both clusters were associated with a decreased activity on the factor 'anterior cingulum and medial frontal gyrus'. The disorganized cluster was characterized by a significant overactivity in the parietal cortex and motor strip and a decreased activity in the corpus callosum. The subsyndromes of chronic schizophrenia are therefore characterized by deviant patterns of cerebral activity rather than deficits in a single location.

Adult↗
PubMed1996

Cholecystokinin receptors in human pancreas and gallbladder muscle: a comparative study.

BACKGROUND & AIMS: Cholecystokinin (CCK) receptors mediate pancreatic secretion and gallbladder contraction. Hitherto, little information on characteristics of CCK receptors in the human pancreas was available. This study identifies CCK receptors in the human pancreas and compares their characteristics with the CCK receptors in the human gallbladder. METHODS: Visualization and quantification of 125I-Bolton-Hunter sulfated CCK octapeptide (125I-BH-CCK-8) binding to tissue sections of the human pancreas and gallbladder were performed by storage phosphor autoradiography. RESULTS: Specific bindings for CCK were visualized in pancreatic tissue and the smooth muscle layer of the gallbladder. Binding of 125I-BH-CCK-8 to the pancreas was inhibited by agonists with the affinities (dissociation constant) of CCK (0.11 nmol/L) approximately gastrin (0.15 nmol/L) and by antagonists with the affinities of CCK-B receptor antagonist (L365,260, 0.18 nmol/L) > CCK-A receptor antagonist (lorglumide, 8.1 nmol/L). In contrast to the pancreas, binding of 125I-BH-CCK-8 to the gallbladder muscle was inhibited with high affinity by CCK-8 and lorglumide but was replaced to a small degree by gastrin and L365,260. CONCLUSIONS: The sub-types of receptors for CCK in the human pancreas and gallbladder are different. The human pancreas predominantly expresses CCK-B receptors, whereas only CCK-A receptors were localized in the human gallbladder muscle.

Adult↗
PubMed1996

Expression of receptors for gut peptides in pancreata of BOP-treated and control hamsters.

The growth of pancreatic cancers may be influenced by certain gut peptides. However, the alteration of gut peptide receptors in the progress of pancreatic carcinogenesis is largely unknown. With storage phosphor autoradiography, this study visualized and characterized receptors for cholecystokinin (CCK), somatostatin (SST), bombesin (BBS), secretin and vasoactive intestinal peptide (VIP) in pancreata of control hamsters (n = 7) and pancreatic preneoplastic lesions (n = 10) or adenocarcinomas (n = 10) of N-nitrosobis(2-oxopropyl)amine (BOP)-treated hamsters. The specific CCK-A and secretin receptors expressed in normal pancreata were markedly reduced in pancreatic preneoplastic lesions and absent in adenocarcinomas. In the development of pancreatic tumours, the subgroup of SST receptors did not change, but both the affinity and binding capacity declined. In comparison with the binding of VIP to normal pancreata, specific VIP binding was significantly lower in preneoplastic lesions and almost absent in pancreatic adenocarcinomas. No specific binding for BBS was detected in normal pancreas or (pre)neoplastic lesions of hamster pancreas. The reduction or absence of receptors for CCK, secretin, SST and VIP in hamster pancreas with the progress of carcinogenesis suggests that in BOP-treated hamsters, pancreatic adenocarcinomas have, to a large extent, lost the hormone-dependent characteristics of the original tissue.

Adenocarcinoma↗
PubMed1996

Biological effects of weak blast waves and safety limits for internal organ injury in the human body.

One hundred and seventeen adult sheep of both sexes, each weighing 15.2-42.4 kg, were used for this study. The purpose of this study was to investigate the relationship of the physical parameters of the waves to internal organ injury by exposing sheep to weak blast waves in TNT (trinitrotoluene) explosions, biological shock tube, and gun muzzle blasts. The results showed that the organ most sensitive to the TNT explosion was the lungs, whereas the upper respiratory tract was most sensitive to muzzle blast waves. The injury thresholds of overpressure were 29.0, 29.5, and 41.2 kPa for upper respiratory tract, lungs, and gastrointestinal tract respectively at a single exposure. Repeated exposure to 60 blasts reduced the injury threshold of the internal organs. The injury thresholds for upper respiratory tract, lungs, and gastrointestinal tract were 21.0, 18.0, and 40.4 kPa, respectively. The duration of overpressure of weak blast waves was 2.4-4.2 milliseconds, which did not significantly affect the severity of injury. The safety limits of weak blast waves to internal organ injury of human body were as follows: Ps = 37-3Ln.Tc.N/4(Tc.N < or = 1000) and Ps = 20.4(Tc.N > 1000). The results suggest that repeated exposures decrease the injury threshold of the internal organs. The safety limits proposed could protect 90% of the exposed population against internal organ injury caused by weak blast waves.

Animals↗
PubMed1996

Visualization and characterization of CCK receptors in exocrine pancreas of rat with storage phosphor autoradiography.

Studies on cholecystokinin (CCK) receptors in rat pancreas are usually performed on homogenates. Using storage phosphor autoradiography, a new imaging technique with a high sensitivity and large linear dynamic range, we visualized and characterized CCK receptors in tissue sections of normal rat pancreas. The density of CCK receptors in pancreatic tissue sections from 10 normal rats appeared to be unevenly distributed and variable in serial sections. The binding of labeled CCK-8 was markedly inhibited by CCK-8 and CCK-A receptor antagonists, but it was only weakly affected by gastrin and CCK-B receptor antagonists. At room temperature the CCK-8 dose-inhibition curve was fitted by a two-site model: one with a high-affinity but low-capacity site and another with a low-affinity but high-capacity site. The CCK-8 dose-inhibition curve showed that the inhibition of the variable high-density receptors took place at a low concentration of CCK-8, while the diffuse low-density receptors were inhibited at the high concentration of 1 microM CCK-8. Binding of labeled CCK-8 at 37 degrees C was homogeneous with a low affinity and comprised only 4% of that found at room temperature. In summary, an uneven density of CCK receptors in the rat exocrine pancreas was observed and attributed to the variable expression of high-affinity CCK receptors in pancreatic acini.

Animals↗
PubMed1996

Initial externalization followed by internalization of beta-adrenergic receptors in rat heart during sepsis.

Changes in the distribution of beta-adrenergic receptors in two subcellular fractions, the sarcolemma and the light vesicle, of rat heart during sepsis were studied, using [3H]dihydroalprenolol ([3H]DHA) binding and photoaffinity labeling with [125I]iodocyanopindolol ([125I]ICYP). Sepsis was induced by cecal ligation and puncture (CLP). Septic rat hearts exhibit an initial hypercardiodynamic (9 h after CLP; early sepsis) and a subsequent hypocardiodynamic (18 h after CLP; late sepsis) state. [3H]DHA-binding studies show that, during early sepsis, the maximum binding capacity (Bmax) was increased by 35% in sarcolemma but was decreased by 25% in light vesicles, whereas during late sepsis, the Bmax was decreased by 39% in sarcolemma but was increased by 30% in light vesicles. Photoaffinity labeling studies show that the incorporation of [125I]ICYP into 64,000-Da peptide during early sepsis was increased by 32% in sarcolemma but was decreased by 27% in light vesicles, whereas during late sepsis, the incorporation was decreased by 30% in sarcolemma but was increased by 35% in light vesicles. These data indicate that beta-adrenergic receptors in the rat heart were externalized from light vesicles to sarcolemma during the hyperdynamic phase but were internalized from surface membranes to intracellular sites during the hypodynamic phase of sepsis. Because beta-adrenergic receptors mediate adrenergic control of cardiac muscle contraction, a biphasic intracellular redistribution of beta-adrenergic receptors in the heart may contribute to the development of the initial hypercardiodynamic and subsequent hypocardiodynamic states during sepsis.

Animals↗
PubMed1996

Seasonal comparison of cytokine profiles in atopic asthmatics and atopic non-asthmatics.

Previous studies have suggested that peripheral blood T cell cytokine release may reflect the situation in the bronchial mucosa in atopic asthmatics. We have therefore examined spontaneous, rye grass pollen-stimulated, and PHA-stimulated secretion of IL-2, IL-4, IL-5, and IFN-gamma in cultures of peripheral blood mononuclear cells (PBMC) from atopic asthmatic, atopic non-asthmatic and normal controls in and out of the rye grass pollen season. Compared to normal controls, both atopic groups showed higher IL-2 and IL-5 production (p < 0.01 and p < 0.05) and higher percentages of CD4 cells expressing CD25 and HLA-DR (p < 0.05) in response to rye grass pollen, elevated IL-4 production in response to PHA (p < 0.01), and a non-significant trend towards lower IFN-gamma production. However, the capacity of PBMC from atopic asthmatics to produce IL-5 was greater than that for atopic non-asthmatics (p < 0.05). Furthermore, seasonal changes in symptom score, FEV1 % predicted, and PD20 methacholine correlated with seasonal elevated production of IL-5 by PBMC in the asthmatic group (r = 0.862, -0.679, and -0.620; p < 0.01, 0.02, and 0.05, respectively). Our results suggest that elevated production of IL-2 and IL-4 and higher percentages of activated CD4 T cells are associated with atopy per se, but elevated production of IL-5 also relates to the clinical expression of atopic asthma.

Adult↗
PubMed1996

Investigation on inhibition of biological effects of endothelin.

The effects of a series of substances on the biological function of endothelin (ET) are reported. The substances used are: synthetic inhibitors of endothelium derived relaxing factors (EDRFs), inhibitor of big-endothelin converting enzyme phosphoramidon, antiserum of endothelin, antagonists of endothelin A receptor BQ123 and JKC301, and two Chinese anti-snake venom herb medicines Lobelia radicans Thumb and Taris polyphylla Smith var. chinensis (Franch) Hara. The results showed that inhibiting the production of nitric oxide (NO) could stimulate ET release from vascular endothelium, elevate plasma ET and increase blood pressure. These changes could be reversed by L-arginine (L-Arg), the substrate of nitric oxide synthase (NOS). The amount of ET released by arterial endothelium could be increased or inhibited by inhibiting or stimulating the synthesis of prostacyclin (PGI2). The plasma ET level and blood pressure in both SHR and WKY rats could be decreased by giving phosphoramidon (PhR). The above results indicate that the biological effects of ET could be antagonized by inhibiting the synthesis or release of ET, decreasing the level of plasma ET, blocking the binding of ET with its receptor and using some Chinese anti-snake venom herb medicines.

Animals↗
PubMed1996

Enforced expression of Bcl-XS induces differentiation and sensitizes chronic myelogenous leukemia-blast crisis K562 cells to 1-beta-D-arabinofuranosylcytosine-mediated differentiation and apoptosis.

Human chronic myelogenous leukemia-blast crisis K562 cells have been demonstrated to be relatively resistant to antileukemic drug-induced apoptosis. This has been attributed to the activity of p210bcr-abl tyrosine kinase present in the K562 cells, which is known to suppress drug-induced apoptosis. Recently, K562 cells have been shown to express the antiapoptosis Bcl-xL but not Bcl-2 proteins. To investigate the contribution of Bcl-xL toward resistance to drug-induced apoptosis, we created K562/Bcl-xS and K562/neo cells by electroporating the expression plasmids pSFFVneo-Bcl-xS and pSFFVneo, containing the bcl-xS and neomycin resistance genes, respectively, into K562 cells. K562/Bcl-xS but not K562/neo cells expressed the bcl-xS mRNA and p19Bcl-xS protein. In contrast, both cell types expressed equivalent levels of Bcl-xL, Bax, Bcl-2, Myc, retinoblastoma, p21cbor-abl, and p145abl proteins. A significant increase in the hemoglobin levels was observed in the K562/Bcl-xS compared with the K562/neo cells (P < 0.05). In addition, K562/Bcl-xS cells were significantly more sensitive than K562/neo cells to undergoing erythroid differentiation induced by low-dose 1-beta-D-arabinofuranosylcytosine (ara-C) and hexamethyl bisacetamide (P < 0.05), but not by all-trans-retinoic acid. Low-dose ara-C- or hexamethyl bisacetamide-induced differentiation was not associated with apoptosis of K562/Bcl-xS or K562/neo cells. Low-dose ara-C-induced erythroid differentiation was accompanied by conversion of the retinoblastoma protein to predominantly its underphosphorylated isoform as well as by down-regulation of Myc levels in K562/Bcl-xS and K562/neo cells. Importantly, exposure to high-dose ara-C (HIDAC; 100 microM ara-C for 4 h) caused internucleosomal DNA fragmentation and the morphological features of apoptosis in K562/Bcl-xS cells. These effects were modestly enhanced by cotreatment with HIDAC plus herbimycin A. In contrast, K562/neo cells were completely resistant to HIDAC- and herbimycin A-induced apoptosis. These results indicate that the expression of Bcl-xS induces erythroid differentiation and partially sensitizes chronic myelogenous leukemia-blast crisis-derived K562 cells to ara-C-induced differentiation and apoptosis.

Antimetabolites, Antineoplastic↗
PubMed1996

[Protective effect of ATP-MgCl2 on gut mucosa in burn rat].

In order to study the protective effect of ATP-MgCl2 on gut mucosal barrier function in trauma-induced stressed animal, full thickness burn of 30% total body surface area (TBSA) was produced in rats, and ATP-MgCl2 was injected intraperitoneally right after scald-injury. Malondialdehyde (MDA) contents of ileum mucosa were determined and morphological alteration in the ileum was observed under light microscope. The results showed that ileum mucosal MDA content increased significantly, accompanied by obvious morphological change, after the injury, whereas MDA content was maintained at the normal control level and pathological alteration in ileum tissue was abated after the use of ATP-MgCl2. It suggests that ATP-MgCl2 possesses a protective effect on gut mucosal barrier function of scald-injured rat, and the mechanism involved may be related to the inhibition of lipid peroxidation in gut mucosa.

Adenosine Triphosphate↗
PubMed1996

[Activation of CD4+ T cells and increased release of interleukin-5 in cultures of bronchoalveolar lavage cells and PBMC from patients with asthma].

To investigate the roles of CD4+ T cells and Th2 cytokine interleukin (IL)-5 in asthma, we examined the activation of CD4+ T cells and IL-5 production in cultures of bronchoalveolar lavage (BAL) cells and PBMC with and without allergen stimulation, in vitro, in 12 atopic asthmatic, 10 non-atopic asthmatic and 9 atopic non-asthmatic patients, as well as 10 normal control subjects. The patients with atopic and non-atopic asthma had significantly increased percentages of CD4+ T cells expressing CD25 (10.1% +/- 1.8% and 10.6% +/- 2.9%) and HLA-DR (11.2% +/- 3.1% and 12.0% +/- 3.6%, respectively) as compared with normal control subjects (P < 0.01) in unstimulated BAL cell cultures. IL-5 levels in the supernatants of those BAL cells from atopic and non-atopic asthmatic patients significantly enhanced (43.8 +/- 14.2 pg/ml and 85.5 +/- 15.1 pg/ml) as compared with those for atopic non-asthmatic and normal control subjects (P < 0.01). Meanwhile, increased percentages of activated CD4+ T cells and IL-5 secretion were also observed in the cultures of unstimulated PBMC from both types of asthmatic patients. In the cultures of allergen-stimulated BAL cells and PBMC, atopic asthmatic patients demonstrated marked increase in the percentage of CD4+ CD25+ T cells (17.9% +/- 13.9% and 29.0% +/- 27.5%) and IL-5 production (30.5 +/- 13.3 pg/ml and 109.3 +/- 35.0 pg/ml, for BAL cell and PBMC cultures respectively) as compared with nona-topic asthmatic patients (P < 0.01). Although the percentages of activated CD4+ T cells and IL-5 secretion elevated significantly in allergen-stimulated culture of PBMC from atopic non-asthmatic subjects, the IL-5 release by the allergen-stimulated BAL cells from the same subjects were still significantly lower than both forms of asthmatic patients (P < 0.01). Our findings show that activation of CD4+ T cells and IL-5 production are strongly implicated in the pathogenesis of both atopic and non-atopic asthma.

Adult↗