Biomedical subjects
Publications and source records attributed to B Kang.
The principal g values of a series of [MOXn]m- (M = VIV, CrV, MoV; X = F-, Cl-, Br-; n = 4, 5; m = 1, 2, 3) complexes are calculated by the INDO-CI-Stone method. The results agree well with the experimental data and reveal that the traditional models have some limitations in calculating g values for some complexes of this type.
Oral administration of antigen induces an antigen-specific immunologic tolerance and many studies are being carried out to apply this phenomenon to the treatment of autoimmune diseases. In this study, we investigated long-term Th1 and Th2 tolerance in mice given a high dose of orally administered Ovalbumin (OVA). Feeding OVA to BALB/c mice suppressed OVA-specific IgG response and the degree of inhibition was dose-dependent in the range of 2.5-250 mg. Moreover, the state of tolerance established by prior feeding of high dose of OVA was present after 26 weeks. Interestingly, even though both Th subsets were tolerized significantly for a short period, the tolerizing effect was more pronounced and persistent in Th2-mediated immune responses. Thus we speculate that oral administration of a single high dose of OVA induces Th1- and Th2-tolerance by different mechanisms. Our findings could be important in the development of therapeutics for the treatment of autoimmune disease and allergy.
We reported previously that Ro-318220 blocked expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) induced by tumor necrosis factor-alpha (TNF-alpha) and subsequently caused apopotosis in mesangial cells (Y.-L. Guo, B. Kang, and J. R. Williamson. J. Biol. Chem. 273: 10362-10366, 1998). These data support our hypothesis that a TNF-alpha-inducible phosphatase may be responsible for preventing sustained activation of c-Jun NH2-terminal protein kinase (JNK) and consequent cell death in these cells (Y.-L. Guo, K. Baysal, B. Kang, L.-J. Yang, and J. R. Williamson. J. Biol. Chem. 273: 4027-4034, 1998). In this study, we investigated the involvement of protein kinase C (PKC) in regulation of MKP-1 expression in mesangial cells together with effects on viability. Although originally characterized as a PKC inhibitor, Ro-318220 inhibited TNF-alpha-induced MKP-1 expression through a mechanism other than blocking the PKC pathway. Furthermore, inhibition of the PKC pathway neither significantly affected TNF-alpha-induced MKP-1 expression nor made cells susceptible to toxic effect of TNF-alpha. Thus PKC activation is not essential for cells to achieve the resistance to TNF-alpha cytotoxicity displayed by normal mesangial cells. However, activation of PKC by phorbol 12-myristate 13-acetate (PMA) dramatically increased cellular resistance to the apoptotic effect of TNF-alpha. Coincidentally, PMA stimulated MKP-1 expression and suppressed JNK activation. Therefore, PMA-induced MKP-1 expression may contribute to the protective effect of PMA. These results provide a mechanistic explanation for previous documentation that PKC activation can rescue some cells from apopotosis.
It has been proposed that ceramide acts as a cellular messenger to mediate tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. Based on this hypothesis, it was postulated that resistance of some cells to TNF-alpha cytotoxicity was due to an insufficient production of ceramide on stimulation by TNF-alpha. The present study was initiated to investigate whether this was the case in mesangial cells, which normally are insensitive to TNF-alpha-induced apoptosis. Our results indicate that although C2 ceramide was toxic to mesangial cells, the cell death it induced differed both morphologically and biochemically from that induced by TNF-alpha in the presence of cycloheximide (CHX). The most apparent effect of C2 ceramide was to cause cells to swell, followed by disruption of the cell membrane. It is evident that C2 ceramide caused cell death by necrosis, whereas TNF-alpha in the presence of CHX killed the cells by apoptosis. C2 ceramide did not mimic the effects of TNF-alpha on the activation of c-Jun NH2-terminal protein kinase and nuclear factor-kappaB transcription factor. Although mitogen-activated protein kinase [extracellular signal-related kinase (ERK)] was activated by both C2 ceramide and TNF-alpha, such activation appeared to be mediated by different mechanisms as judged from the kinetics of ERK activation. Furthermore, the cleavage of cytosolic phospholipase A2 during cell death induced by C2 ceramide and by TNF-alpha in the presence of CHX showed distinctive patterns. The present study provides evidence that apoptosis and necrosis use distinctive signaling machinery to cause cell death.
Previously we showed that rat mesangial cells are normally resistant to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. They are made susceptible to the apoptotic effect of TNF-alpha when pretreated with actinomycin D, cycloheximide or vanadate. A sustained c-Jun N-terminal protein kinase (JNK) activation was closely correlated with the initiation of apoptosis under these conditions. We proposed that a TNF-alpha-inducible phosphatase was responsible for preventing a sustained activation of JNK and consequent apoptosis in these cells (Guo, Y.-L., Baysal, K., Kang, B. , Yang, L.-J., and Williamson, J. R. (1998) J. Biol. Chem. 273, 4027-4034). In the present study we provide further evidence to support this hypothesis. Ro318220, although originally identified as a specific inhibitor of protein kinase C, was subsequently found to be a strong inhibitor of MKP-1 expression. In rat mesangial cells, pretreatment of the cells with Ro318220 blocked expression of MKP-1 induced by TNF-alpha. This treatment also prolonged JNK activation and caused apoptosis. Taken together, our results support the currently controversial hypothesis that the JNK pathway is involved in TNF-alpha-induced apoptosis. In addition, we provide a mechanistic explanation for how mesangial cells in primary culture achieve resistance to TNF-alpha cytotoxicity. Specifically, induction of MKP-1 by TNF-alpha appears to be responsible for protection of the cells from apoptosis by preventing a prolonged activation of JNK.
Rat mesangial cells are normally resistant to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. In this report we show that the cells can be made susceptible to the apoptotic effect of TNF-alpha when pretreated with actinomycin D, cycloheximide, or vanadate. c-Jun N-terminal protein kinase (JNK) has been thought to mediate apoptotic processes elicited by some stimuli, but its involvement in TNF-alpha-induced apoptosis has been controversial. JNK activation was investigated under conditions where the mesangial cells were either resistant or susceptible to TNF-alpha-induced apoptosis. TNF-alpha alone stimulated a single transient JNK activity peak. However, when the cells were pretreated with actinomycin D or cycloheximide, TNF-alpha stimulated a second sustained JNK activity peak. When the cells were pretreated with the phosphatase inhibitor vanadate, TNF-alpha-induced JNK activation was greatly prolonged. In all three cases, a sustained JNK activation was associated with the initiation of apoptosis. Our data suggest that a sustained activation of JNK induced by these reagents may be associated with blocking the expression of a phosphatase that inactivates JNK. Further studies reveal that the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) was induced by TNF-alpha, indicating that MKP-1 may be involved in protecting the cells from apoptosis by preventing a prolonged activation of JNK under normal conditions. Additional studies showed that extracellular signal-regulated protein kinase activation stimulated by TNF-alpha was unlikely to contribute to the resistance of mesangial cells to TNF-alpha cytotoxicity.
AIM: To study the influences of cyproheptadine (Cyp) on the endocrine functions of pituitary-thyroid axis and pancreatic beta cells in rats. METHODS: The effects of Cyp on functions of pituitary-thyroid axis and pancreatic beta cells were observed by radioimmunoassay, biochemical analysis, and electron microscope. RESULTS: Cyp 2.3 mg.kg-1 ig for 10 d decreased serum thyroid stimulating hormone (TSH) from control groups (5.3 +/- 0.9) to (4.2 +/- 0.9) mU.L-1 and insulin levels from (64 +/- 8) to (50 +/- 9) kIU.L-1 (P < 0.05 and 0.01). Cyp 4.6 mg.kg-1 decreased serum TSH (3.8 +/- 0.5) mU.L-1, T3 (1.2 +/- 0.2) mmol.L-1, T4 (62 +/- 7) mmol.L-1, and insulin levels (42 +/- 8) kIU.L-1 decreased (P < 0.05 or 0.01). The retrograde changes of ultrastructure of pituitary TSH cells and pancreatic beta cells. CONCLUSION: Cyp has an inhibiting action on endocrine functions of pituitary-thyroid axis and pancreatic beta cells in rats.
Activation of the thrombin receptor provides a strong mitogenic signal in CCL39 cells. Ceramide was found to inhibit thrombin-mediated mitogenesis in these cells while dihydroceramide had no effect. Many growth inhibitors exert their effect by inhibiting extracellular signal-regulated kinase (ERK) signaling pathway. However, neither ceramide nor dihydroceramide blocked the thrombin-induced activation of ERK. In contrast, both agents potentiated ERK activity. The expression of c-fos, c-jun and cyclin D1, which are downstream of ERK in the mitogenic pathway were stimulated by thrombin but this stimulation was not affected by ceramide or dihydroceramide. Therefore, the ceramide inhibition of thrombin-stimulated cell growth in CCL39 cells does not appear to be mediated by an effect on the activation of ERK. Furthermore, the data also suggest that the separate effects of ceramide on thrombin-stimulated cell growth and ERK activity are mediated by different mechanisms.
Presented in this paper are the results of ultrasonic examination in 29 cases of hemangiomas of soft tissue. Out of the 29 cases, 20 lesions were revealed as heterogeneous echoic masses; 6 as anechoic areas and 3 as solid masses. Hyperechoic foci of calcifications or phlebolithes were detected in 16 cases. Intramuscular hemangiomas were sonographically diagnosed in 15 patients; hemangiomas of soft tissue in 8, pseudoaneurysm in 3; deformity of the arteriovenous fistula in 1 and hemangiosarcoma in 2. The diagnosis in 28 patients were surgically and pathologically confirmed and the remaining one was confirmed by aspiration and cytological examination. The diagnostic accuracy of the ultrasound was 100%.
The effects of captopril, and angiotensin converting enzyme (ACE) inhibitor, on responses to bradykinin (BK), to angiotensin (Ang) I and II, and to other agonists were investigated in the hindquarters vascular bed of the rat. Under conditions of controlled flow, intra-arterial (i.a.) injections of BK in doses of 0.1-1.0 microgram, produced dose related decreases in hindquarters perfusion pressure and evoked decreases in systemic arterial pressure. Intra-arterial injections of Ang I and II produced dose-related increases in hindquarters perfusion pressure. Following administration of captopril in a dose of 2 mg/kg i.v., vasodilator responses to i.a. injections of BK were only slightly enhanced in the hindquarters vascular bed, whereas the evoked systemic vasodepressor responses to i.a. injections of BK were markedly enhanced by the ACE inhibitor. Captopril significantly reduced vasoconstrictor responses to i.a. injections of Ang I, whereas vasoconstrictor responses to i.a. injections of Ang II were significantly enhanced. The ACE inhibitor did not significantly alter vasodilator responses to i.a. injections of acetylcholine, nitroglycerin, nitric oxide, albuterol, or pinacidil. The present data show that BK has potent vasodilator activity in the hindquarters vascular bed of the rat and suggest that the site of action is most likely upstream from the site of inactivation, whereas the site of action of Ang I is at or near the site of conversion to Ang II in the hindquarters vascular bed. The observation that the evoked systemic vasodepressor responses to i.a. injections of BK were greatly enhanced, suggest that the lung is the major site of inactivation of BK.
The mechanism by which bradykinin (BK) decreases vascular resistance was investigated in the hindquarters vascular bed of the rat. Under conditions of controlled blood flow, BK produced dose-related decreases in hindquarters perfusion pressure when injected into the perfusion circuit in doses of 0.1-1.0 pg. Responses to BK were reproducible with respect to time, and HOE-140 (D-Arg, [Hyp3,Thi5,D-Tic7,Oic8] -BK), a kinin B2 receptor antagonist, decreased hindquarters vasodilator responses to the peptide. HOE-140 had no significant effect on responses to vasodilator agents, which act by a variety of pharmacologically distinct mechanisms. Nitric oxide synthase inhibitors N(omega)-nitro-L-arginine methyl ester or N(omega)-nitro-L-arginine benzyl ester did not decrease responses to BK in doses that decreased hindquarters vasodilator responses to acetylcholine. The cyclooxygenase inhibitors meclofenamate and indomethacin had no effect on responses to BK in doses that attenuated vasodilator responses to the prostaglandin precursor, arachidonic acid. Clotrimazole or 5,8,11,14-eicosatetraynoic acid (ETYA), cytochrome P-450 arachidonic acid metabolism inhibitors, in doses that attenuated vasodilator responses to arachidonic acid, had no effect on responses to BK. Glybenclamide or U-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl), K+-ATP channel antagonists, in doses that attenuated responses to lemakalim, had no significant effect on responses to BK. Finally, des-Arg9-BK, a reported kinin B1 receptor agonist, decreased hindquarters perfusion pressure when injected in doses of 3-30 microg, and responses to the B1 agonist were attenuated by HOE-140. The observation that des-Arg9-BK, in high doses, induces modest HOE-140-sensitive responses suggests that kinin B1 receptors are not normally expressed in the hindquarters vascular bed of the rat. The present results indicate that BK dilates the hindquarters vascular bed by a kinin B2 receptor mechanism that is independent of the release of nitric oxide, cyclooxygenase, or P-450 metabolites of arachidonic acid or the activation of K+-ATP channels.
BACKGROUND: Responses to proadrenomedullin NH(2)-terminal 20 peptide (PAMP), a novel hypotensive peptide formed from preproadrenomedullin, and the effects of inhibition of adrenergic vasomotor tone with the alpha-receptor antagonist, phenolamine, on responses to PAMP were investigated in the systemic and hindquarters vascular bed of the rat. METHODS AND RESULTS: Intravenous injections of PAMP decreased systemic arterial pressure and in the hindquarters vascular bed of the rat under conditions of controlled hindquarters blood flow, intra-arterial injections of PAMP decreased perfusion pressure in a dose-related manner. Following administration of the alpha receptor blocking agent, phenotlamine, systemic depressor and hindquarters vasodilator responses to PAMP were not significantly decreased, whereas phentolamine significantly decreased systemic and hindquarters pressor responses to norepinephrine. Phentolamine had no significant effect on vasodilator responses to bradykinin, albuterol, or to nitroglycerin. CONCLUSIONS: The present data show that PAMP has significant systemic vasodepressor and vasodilator activity in the hindquarters vascular bed of the rat and suggest that vasodepressor and hindquarters vasodilator responses to PAMP are not dependent upon the presence of adrenergic vasomotor tone.
This paper presents the results of sonographic and radiographic examinations in 48 patients clinically diagnosed as having bone tumors. Sonography revealed bone destruction in all 48 cases, elevated periosteum in 26 cases and soft tissue mass in 34 cases. The results obtained in this series demonstrate that most bone tumors have their characteristic sonographic features such as giant cell tumors, malignant bone tumors, bone cysts, as well as metastatic lesions. Study showed that sonography has equally high accuracy in the diagnosis of these tumors compared with radiography.
Previously, studies have demonstrated that the effects of both a laboratory-produced vancomycin and a clinically available vancomycin were mediated, in part, by activation of both H(1) and H(2) receptors; however, other mechanisms may play a role in the vascular changes associated with vancomycin, since neither H(1) and H(2) receptor blockade has completely abolished the vasodilator responses to vancomycin in any model system. To study the mechanisms of vancomycin interactions in the hindlimb vascular bed of the rat, responses of two types of vancomycin preparations were studied. Vancomycin prepared for either clinical or laboratory use produced an initial short-lived period of vasoconstriction followed by a prolonged period of vasodilation in the hindlimb vascular bed. Responses to both the vancomycins and histamine on systemic arterial vasodilation were significantly decreased after administration of both the H(1)-receptor antagonist diphenhydramine and the H(2)-receptor antagonist famotidine. Verapamil, an L-type calcium channel blocker, significantly reduced the vasopressor responses to clinical vancomycin but not the vasopressor responses to laboratory vancomycin. Enalaprilat, and angiotensin-converting enzyme blocker, significantly reduced the vasodilator responses but not the vasoconstrictor responses of clinical vancomycin and significantly reduced the vasoconstrictor responses but not the vasodilator responses to laboratory vancomycin. Meclofenamate, a cyclo-oxygenase inhibitor, and N(omega)-L-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthetase inhibitor, had no significant effect on the biphasic responses with either vancomycin preparations. Atropine, an anticholinergic-antimuscarinic receptor antagonist, and propranolol, a beta adrenergic blocker, had no significant effect on vancomycin responses. Finally, ondansetron, a serotonin receptor blocker, and HOE 140, a bradykinin receptor blocker, also had no significant effect on vancomycin responses. These data suggest that both vancomycin preparations (clinically available and laboratory prepared) caused biphasic responses that differed from the dose-dependent vasodilation elicited by histamine. Both vancomycin preparations' vasodilator responses appear to be modulated, in part, by a histamine receptor--sensitive mechanism, while vancomycin-induced vasoconstrictor responses appear to be modulated, in part, by angiotensin-converting enzyme and L-type calcium channel--sensitive mechanisms in the rat hindlimb vascular bed. These data also suggest that the vascular responses of vancomycin are preparation dependent.
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A clinical study of 67 female schizophrenics was conducted. Thirty two patients of them treated with the Shuizhi (leech)-Dahuang (rhubarb) mixture mainly with low dosage of antipsychotic drugs (combined therapy group), while other 35 cases were treated with antipsychotic drugs only (control group). The result showed that their overall therapeutic effects were similar and the combined therapy group could reduce the dosages of antipsychotic drugs and its side effects, and tended to normalize the hemorheologic indices.
The effects of aprotinin on mean arterial pressure, carotid artery blood flow, pulmonary vascular resistance, and systemic vascular resistance have not been well documented. Therefore, the responses of aprotinin on the mean arterial pressure, carotid artery blood flow and the changes in pulmonary and hindlimb vascular resistances were investigated in the rat using ultrasonic flow probe analysis, and in two isolated vascular bed preparations. In studies on cardiac output using ultrasonic flow analysis, injections of aprotinin, in doses of 70-7000 KIU intravenously (iv), resulted in no changes in carotid artery ultrasonic flow, suggesting no changes in cardiac output. In isolated blood-perfused lung studies under conditions of controlled pulmonary blood flow, aprotinin, in doses of 7-7000 KIU intra-arterially (ia), caused no significant changes in pulmonary arterial perfusion pressure. Aprotinin, in doses of 7-240 KIU, was injected iv into the hindquarters perfusion circuit, and hindquarters arterial perfusion pressure did not change. Additionally, in the hindquarters perfusion preparation, aprotinin, in doses of 70-7000 KIU, ia resulted in no changes in mean arterial pressure. The present data demonstrate aprotinin has no significant response in MAP, carotid artery blood flow, pulmonary vascular resistance, or hindlimb vascular resistance in the rat.
Vancomycin is known to cause vasodilation, and hypotension secondary to histamine release. We studied the actions of two forms of vancomycin, a clinically available preparation, clinical vancomycin, and a research grade preparation, laboratory vancomycin, in the presence of an H1 receptor blockade and during H2 receptor blockade with Doppler flow probe analysis of carotid artery flow rate. Clinical vancomycin, laboratory vancomycin, and histamine, increased the mean carotid artery blood flow from baseline in a dose-dependent manner. Diphenhydramine, H1 receptor antagonist, attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin and for each dose of histamine. Famotidine, H2 receptor antagonist, significantly attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin, the two higher doses of laboratory vancomycin, and with each dose of histamine. Both diphenhydramine and famotidine attenuated the increase of mean carotid artery blood flow with clinical vancomycin, laboratory vancomycin, and histamine. These data suggest that the change in carotid flow produced by vancomycin, is dependent, in part, on either H1 or H2 receptor activation.