共查询到20条相似文献,搜索用时 31 毫秒
1.
Hepatoprotectivity of Panduratin A against liver damage: In vivo demonstration with a rat model of cirrhosis induced by thioacetamide
下载免费PDF全文
![点击此处可从《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Suzy M. Salama Ibrahim Abdel Aziz Ibrahim Naiyer Shahzad Saeed Al‐Ghamdi Nahla Ayoub Ahmed Salim AlRashdi Mahmood Ameen Abdulla Nur'Ain Salehen Mehmet Bilgen 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2018,126(9):710-721
This experiment evaluated Panduratin A (PA), a chalcone isolated from Boesenbergia rotunda rhizomes, for its hepatoprotectivity. Rats were subjected to liver damage induced by intra‐peritoneal injection of thioacetamide (TAA). PA was tested first for its acute toxicity and then administered by oral gavage at doses 5, 10, and 50 mg/kg to rats. At the end of the 8th week, livers from all rats were excised and evaluated ex vivo. Measurements included alkaline phosphatase (AP), alanine transaminase (ALT), aspartate transaminase (AST) and gamma‐glutamyl transferase (GGT), serum platelet‐derived growth factor (PDGF) and transforming growth factor (TGF‐β1), and hepatic metalloproteinase enzyme (MMP‐2) and its inhibitor extracellular matrix protein (TIMP‐1). Oxidative stress was measured by liver malondialdehyde (MDA) and nitrotyrosine levels, urinary 8‐hydroxy 2‐ deoxyguanosine (8‐OH‐dG), and hepatic antioxidant enzyme activities. The immunohistochemistry of TGF‐β1 was additionally performed. PA revealed safe dose of 250 mg/kg on experimental rats and positive effect on the liver. The results suggested reduced hepatic stellate cells (HSCs) activity as verified from the attenuation of serum PDGF and TGF‐β1, hepatic MMP‐2 and TIMP‐1, and oxidative stress. The extensive data altogether conclude that PA treatment could protect the liver from the progression of cirrhosis through a possible mechanism inhibiting HSCs activity. 相似文献
2.
Relevance of spontaneous fabT mutations to a streptococcal toxic shock syndrome to non‐streptococcal toxic shock syndrome transition in the novel‐type Streptococcus pyogenes isolates that lost a salRK
下载免费PDF全文
![点击此处可从《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ichiro Tatsuno Ryo Okada Masakado Matsumoto Nanako Hata Hideyuki Matsui Yan Zhang Masanori Isaka Tadao Hasegawa 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2016,124(5):414-424
3.
L. Grahnquist M. Chen A. Gerasev R. Aizman G. Celsi 《Acta physiologica (Oxford, England)》2001,171(2):145-151
The role of angiotensin subtype‐1 (AT1) and ‐2 (AT2) receptors in mediating the effects of angiotensin II (ANG II) on several K+ transporters was studied in rat distal colon using an Ussing chamber. Angiotensin II induced K+ secretion at two different doses. Secretion occurred at 10–8 and 10–4 M , as a result of an increase in serosal‐to‐mucosal flux (Js–m). The ANG II‐induced stimulation of Js–m at a low dose (10–8 M ) was abolished by PD123319 while losartan did not alter the low‐dose ANG II‐dependent increase in Js–m. In contrast, the increase in Js–m induced by a high‐dose of ANG II (10–4 M ) was blocked by losartan, whereas PD123319 partially reduced the stimulatory effect. In the presence of both blockers, high‐dose ANG II induced an inhibition of basal Js–m. Low‐dose ANG II activated the barium‐sensitive K+ channels, whereas the Na+, K+, 2Cl– cotransporter and the Na+, K+‐ATPase pump were unchanged. At the high dose, ANG II activated the barium‐sensitive K+ channels and the Na+, K+, 2Cl– cotransporter and inhibited the Na+, K+‐ATPase pump. These data indicate that ANG II stimulates serosal‐to‐mucosal K+ flux in the rat distal colon at high and low doses via different receptors and K+ transporters. 相似文献
4.
Haixia Liu Mingrui Zheng Jianou Qiao Yajie Dang Pengyu Zhang Xianqiao Jin 《Immunology》2014,142(1):78-88
Aspergillus fumigatus is often associated in asthmatic patients with the exacerbation of asthma symptoms. The pathomechanism of this phenomenon has not been fully understood. Here, we evaluated the immunological mechanisms and the role of the prostaglandin D2/ Chemoattractant Receptor‐Homologous Molecule Expressed on Th2 Cells (CRTH2) pathway in the development of Aspergillus‐associated asthma exacerbation. We studied the effects of A. fumigatus on airway inflammation and bronchial hyper‐responsiveness in a rat model of chronic asthma. Inhalation delivery of A. fumigatus conidia increased the airway eosinophilia and bronchial hyper‐responsiveness in ovalbumin‐sensitized, challenged rats. These changes were associated with prostaglandin D2 synthesis and CRTH2 expression in the lungs. Direct inflammation occurred in ovalbumin‐sensitized, challenged animals, whereas pre‐treatment with an antagonist against CRTH2 nearly completely eliminated the A. fumigatus‐induced worsening of airway eosinophilia and bronchial hyper‐responsiveness. Our data demonstrate that production of prostaglandin D2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenic factors responsible for the A. fumigatus‐induced enhancement of airway inflammation and responsiveness. 相似文献
5.
6.
AVP not only increases osmotic water permeability (Pf) in the rat cortical collecting duct (CCD), but also acts synergistically with aldosterone to augment sodium reabsorption (JNa). These effects are inhibited by catecholamines via α2 adrenergic receptors, and by dopamine. We review here studies designed to determine the mechanism and receptor involved in dopamine action. The inhibitory effect of dopamine on Na+ and water transport was found to be reversible, and was not produced by agonists specific to D1A and D1B receptors. D2‐type (D2, D3 or D4) receptors and activation of the GTP‐binding protein Gi were implicated by the observation that dopamine had no inhibitory effect when JNa and Pf were stimulated by a cyclic AMP analogue plus isobutylmethylxanthine. The only dopaminergic antagonist that reversed the inhibitory effect of dopamine was clozapine, which is relatively D4‐specific. We also found that dopamine or D1‐specific agonists by themselves had no effect on cAMP production. However, dopamine inhibited the high rate of AVP‐dependent cAMP production, and this effect of dopamine was reversed by clozapine but not other antagonists or by inhibitors of protein kinase C. The D4 receptor was observed in western blots of renal cortical proteins, and it was localized to the collecting duct by RT‐PCR and immuno‐histochemistry using a D4‐specific antibody. These results show that at least a portion of the natriuretic effect of dopamine can be attributed to inhibition of AVP‐dependent Na+ reabsorption by the CCD, and they introduce another signalling system as a candidate in the aetiology of low‐renin, salt‐dependent hypertension. 相似文献
7.
Ide Boushel Srensen Fernandes Cai Pott Secher 《Acta physiologica (Oxford, England)》2000,170(1):33-38
A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA Vmean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA Vmean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg?1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA Vmean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA Vmean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s?1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min?1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min?1) and ΔMCA Vmean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s?1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA Vmean (10.2 ± 2.5 cm s?1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system. 相似文献
8.
目的:研究2型糖尿病大鼠早期血清心肌肌钙蛋白I(cTnI)的水平及心功能变化,探讨早期2型糖尿病大鼠血清cTnI水平与糖尿病心肌损伤发生发展之间的关系,明确cTnI在糖尿病心肌病发生发展中的作用。方法:通过高脂饮食联合链脲佐菌素建立2型糖尿病大鼠模型,实验将大鼠分为正常对照组、糖尿病2周模型组及4周模型组,超声心动图检测心功能相关指标,血清检测空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、空腹胰岛素(FINS)及cTnI水平,HE染色法观察心肌病理结构变化,Western blot法检测心肌cTnI蛋白表达变化,通过上述指标变化分析2型糖尿病大鼠早期血清cTnI与大鼠心功能改变之间的关系。结果:与正常组比较,2型糖尿病大鼠TC、TG、LDL-C水平显著升高,HDL-C水平显著降低;糖尿病大鼠4周模型组与2周模型组相比较,TC、TG、LDL-C水平升高更明显,HDL-C水平降低更显著(P0.01);显微镜下糖尿病组大鼠心肌可见局灶性心肌细胞变性、坏死;糖尿病组大鼠相对于正常对照组血清及心肌cTnI表达显著增加(P0.01),且4周模型组比2周模型组增加更明显。结论:糖尿病大鼠早期即出现cTnI水平升高和心功能改变,有望为糖尿病心肌病的早期诊断和治疗提供理论依据。 相似文献
9.
A. Eltayb S. Lindblom S. Oerther S. Ahlenius 《Acta physiologica (Oxford, England)》2001,172(3):205-209
The objective of this study was to examine possible interactions between serotonergic and dopaminergic agents lowering core temperature via stimulation of 5‐HT1A and dopamine (DA) D2 receptors, respectively. The effects of the 5‐HT1A receptor agonist (±)‐8‐hydroxy‐2‐(di‐n‐propylamino)tetralin HBr (8‐OH‐DPAT) and the DA D2/3 receptor agonist 7‐OH‐DPAT on core temperature was monitored in adult male Wistar rats, approximately 300 g body weight. The temperature probe was connected to a PC‐assisted temperature instrument, and an automated printer device was activated when the temperature reading had stabilized (±0.1 °C) for 10 s. As expected, 7‐OH‐DPAT [0.5 and 2.0 μmol kg–1 subcutaneous (s.c.)] as well as 8‐OH‐DPAT (0.15–2.4 μmol kg–1 s.c.), produced a dose‐dependent hypothermia. When combined, there were additive effects of the two compounds, although the effects of 7‐OH‐DPAT were attenuated by 8‐OH‐DPAT at the higher doses (0.6–2.4 μmol kg–1), in all probability because of emerging DA D2 receptor blocking properties of the latter compound. 相似文献
10.
11.
Oseltamivir and indomethacin reduce the oxidative stress in brain and stomach of infected rats
下载免费PDF全文
![点击此处可从《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》网站下载免费的PDF全文](/ch/ext_images/free.gif)
David Calderón Guzmán Maribel Ortiz Herrera Norma Osnaya Brizuela Gerardo Barragán Mejía Ernestina Hernández García Hugo Juárez Olguín Norma Labra Ruíz Armando Valenzuela Peraza 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2018,126(2):128-134
The aim of this study was to determine the effect of oseltamivir and indomethacin on lipid peroxidation (LP), GABA levels, and ATPase activity in brain and stomach of normal and infected rats (IR), as novel inflammation model. Female Sprague Dawley rats grouped five each, either in the absence or presence of a live culture of Salmonella typhimurium (S. typh), were treated as follows: group 1 (control), PBS buffer; group 2, oseltamivir (100 mg/kg); group 3, indomethacin (67 μg/rat); group 4, oseltamivir (100 mg/kg) + indomethacin (67 μg/rat). All drugs were given intraperitoneally for 5 days. IR received the same treatments and the brain and stomach of the rats were removed in order to measure levels of GABA, LP, and total ATPase, using validated methods. Levels of GABA increased in stomach and cortex of IR with oseltamivir, but decreased in striatum and cerebellum/medulla oblongata of IR with indomethacin. LP decreased in the three brain regions of IR with oseltamivir. ATPase increased in stomach of IR and non‐IR with oseltamivir and in striatum and cerebellum/medulla oblongata of IR with indomethacin. Results suggest that the effect of free radicals produced in an infection and inflammatory condition caused by S. typh could be less toxic by a combination of oseltamivir and indomethacin. 相似文献
12.
Endothelium‐dependent hyperpolarizing factor (EDHF) is a powerful vasodilator influence in small resistance arteries and thus an important modulator of blood pressure and flow. As the name suggests, EDHF was thought to describe a diffusible factor stimulating smooth muscle hyperpolarization (and thus vasodilatation). However, this idea has evolved with the recognition that a factor can operate alongside the spread of hyperpolarizing current from the endothelium to the vascular smooth muscle (VSM). As such, the pathway is now termed endothelium‐dependent hyperpolarization (EDH). EDH is activated by an increase in endothelial [Ca2+]i, which stimulates two Ca2+‐sensitive K channels, SKCa and IKCa. This was discovered because apamin and charybdotoxin applied in combination blocked EDHF responses, but iberiotoxin – a blocker of BKCa – was not able to substitute for charybdotoxin. SKCa and IKCa channels are arranged in endothelial microdomains, particularly within projections towards the adjacent smooth muscle, which are rich in IKCa channels and close to interendothelial gap junctions where SKCa channels, are prevalent. KCa activation hyperpolarizes endothelial cells, and K+ efflux through them can act as a diffusible ‘EDHF’ by stimulating VSM Na+,K+‐ATPase and inwardly rectifying K channels (KIR). In parallel, hyperpolarizing current spreads from the endothelium to the smooth muscle through myoendothelial gap junctions located on endothelial projections. The resulting radial EDH is complemented by the spread of ‘conducted’ hyperpolarization along the endothelium of arteries and arterioles to affect conducted vasodilatation (CVD). Retrograde CVD effectively integrates blood flow within the microcirculation, but how the underlying hyperpolarization is sustained is unclear. 相似文献
13.
Excessive exercise may lead to skeletal muscle cell damage with degradation of cellular components and leakage of intracellular enzymes. Calcium has repeatedly been proposed to be involved in these processes. Studies have shown that the resting level of cytoplasmic Ca2+ increases up to threefold during long‐term low‐frequency stimulation. We have shown that electrical stimulation produces a marked increase in Ca2+ uptake and Ca2+ content in rat skeletal muscle, both in vivo and in vitro. Continuous stimulation for 240 min at 1 Hz results in an increased release (18‐fold) of lactate dehydrogenase (LDH) from extensor digitorum longus (EDL) muscle. This was associated with an increased total Ca2+ content (185%), was augmented at high [Ca2+]o and suppressed at low [Ca2+]o. The release of LDH may reflect partial loss of sarcolemmal integrity as a result of degradation of membrane components by Ca2+‐activated enzymes (e.g. calpain or phospholipase A2). After cessation of stimulation the increased release of LDH continues for at least 120 min. This is associated with an up to sevenfold increase in 45Ca uptake. The increased permeability to Ca2+ may further activate calpain and phospholipase A2 and accelerate the loss of membrane integrity. Stimulation‐induced uptake of Ca2+ and release of LDH is most pronounced in EDL (mainly composed of fast‐twitch fibres at variance with soleus which is mainly composed of slow‐twitch fibres). This may account for the observation that prolonged exercise leads to preferential damage to fast‐twitch fibres. We hypothesize that excessive exercise may lead to an intracellular accumulation of Ca2+ and increased cytoplasmic Ca2+ causing activation of self‐accelerating degradative pathways leading to muscle damage. 相似文献
14.
K. Dežman P. Korošec H. Rupnik M. Rijavec 《International journal of immunogenetics》2017,44(5):212-218
We have recently showed that filaggrin (FLG) mutations are associated only with early‐onset of AD, but not with late‐onset of AD. Consequently, other susceptibility genes should receive attention, especially in patients with late‐onset of AD. Our aim was to assess the associations between development of AD and the polymorphisms rs2303067 in SPINK5 and rs490928 in CHI3L1. A study population of 241 AD patients and 164 healthy controls was genotyped for two polymorphisms (rs2303067 in SPINK5 and rs490928 in CHI3L1). Rs2303067 in SPINK5 was significantly associated with early‐onset AD (≤8 years: p = .003; OR = 2.57) and was characterized by the need for hospitalization (p = .006; OR = 2.76), prolonged duration (≥10 years; p = .008; OR = 2.32) and more body parts affected (p = .015; OR = 2.01). In contrast, rs490928 in CHI3L1 was associated with late‐onset AD (>8 years: p = .048; OR = 1.65) and was characterized by no need for hospitalization (p = .049; OR = 1.59), shorter duration (<10 years; p = .017; OR = 1.94) and fewer body parts affected (p = .049; OR = 1.75). Our results confirmed that different AD phenotypes, specifically early‐ and late‐onset AD, have different genetic backgrounds. Early‐onset AD was associated with rs2303067 in SPINK5, which is involved in skin barrier functioning, and late‐onset was associated with rs4950928 in CHI3L1, which is involved in the immune response. Future studies should examine the early‐ versus late‐onset subgrouping more closely. 相似文献
15.
Intracerebroventricular (ICV) angiotensin (AIl) administration stimulates central AII receptors to induce water consumption in rats. The aim of this study was to determine the role of brain AT1 and AT2 receptors in mediating chronic ICV AII‐induced drinking in rats raised on normal or high sodium chloride diets from weaning. Rats were weaned at 21 days of age and placed on normal or high sodium chloride diet for 10–12 weeks. At adulthood, the animals were instrumented with brain lateral ventricular cannulas and femoral arterial catheters. Low dose chronic central AII infusion (20 ng min?1) significantly (P < 0.05) increased water intake in both groups of rats when compared with their respective controls of 24 h artificial cerebrospinal fluid infusions. In a separate group of high sodium fed rats, coinfusion of AII with the AT1 receptor antagonist, losartan (0.25 μg min?1) or the AT2 receptor blocker, PD 123319 (0.50 μg min?1) blocked chronic ICV AII‐induced drinking. Upon reinfusion of AII water intake increased above control. Following the cessation of AII infusions, water intake returned to values not significantly different from control (P > 0.05). In contrast, in the normal sodium fed rats losartan, but not PD 123319, blocked the AII‐mediated water intake. The data demonstrate that in high sodium chloride fed rats AII stimulates both central AT1 and AT2 receptors to induce drinking, while in the normal sodium chloride fed rats the peptide activates the drinking response primarily by stimulation of central AT1 receptors. 相似文献
16.
Mario Juarez‐Ortega Víctor G. Hernandez Patricia Arce‐Paredes Enrique B. Villanueva Miguel Aguilar‐Santelises Oscar Rojas‐Espinosa 《International journal of experimental pathology》2015,96(1):31-41
Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial‐specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG‐inoculated and MLM‐inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell‐mediated immune response (CMI) that was temporary in the MLM‐inoculated group and long‐lasting in the BCG‐inoculated group. DLE were prepared from the spleens of MLM‐ and BCG‐inoculated mice at the peak of CMI. Independent MLM intradermally‐inoculated groups were treated every other day with HLT‐DLE, BCG‐DLE or MLM‐DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 106 splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy. 相似文献
17.
A randomized,double‐blind,placebo‐controlled,dose‐finding trial with Lolium perenne peptide immunotherapy
下载免费PDF全文
![点击此处可从《Allergy》网站下载免费的PDF全文](/ch/ext_images/free.gif)
R. Mösges E. M. Kasche E. Raskopf J. Singh L. Sohlich A. Astvatsatourov K. Shah‐Hosseini S. Pirotton L. Haazen S. R. Durham T. Legon G. Zadoyan M. H. Shamji 《Allergy》2018,73(4):896-904
Background
A novel subcutaneous allergen immunotherapy formulation (gpASIT+?) containing Lolium perenne peptides (LPP) and having a short up‐dosing phase has been developed to treat grass pollen–induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety.Methods
This prospective, double‐blind, placebo‐controlled, phase IIb, parallel, four‐arm, dose‐finding study randomized 198 grass pollen–allergic adults to receive placebo or cumulative doses of 70, 170 or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen–specific immunoglobulins were analysed before and after treatment.Results
Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per‐protocol set). Also, 39% of patients in the 170‐μg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen‐binding assays revealed a highly significant (P < .001) dose‐dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG4 levels increased to 1.6‐fold (70 μg), 3.1‐fold (170 μg) and 3.9‐fold (370 μg) (mPP).Conclusion
Three‐week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.18.
H. Kögler Christian Plathow Eman Al-Hillawi Ian P. Trayer J. Caspar Rüegg 《Pflügers Archiv : European journal of physiology》1998,436(3):398-406
We extracted troponin-I (TnI) from skinned rat and rabbit soleus muscle fibres using a modification of the method described
by Strauss et al. (FEBS Lett 310:229–234, 1992) for replacement of TnI in cardiac preparations. Incubation of soleus muscle fibres with 10 mmol/l vanadate
virtually completely abolished the Ca2+dependence of force. Immunoblot analysis revealed that more than 80% of TnI had been extracted from the preparations. The
Ca2+dependence of force was restored by incubation with a complex of cardiac TnI (cTnI) and troponin-C (cTnC). We examined the
effects of the Ca2+-sensitizing compound EMD 53998 on isometric tension in native porcine cardiac and rabbit soleus skinned fibres as well as
soleus in which the endogenous slow skeletal TnI (ssTnI) had been replaced by cTnI (soleus–cTnI). It was found that 10 μmol/l
EMD 53998 in native soleus increased maximum Ca2+-activated force to 120±1.4% of control. In soleus–cTnI fibres, maximum force was increased to only 105±0.9%, which was similar
to the effect observed in cardiac muscle (108±0.6%). In cardiac muscle, 10 μmol/l EMD 53998 induced a leftward shift of the
pCa-tension relation by 0.65 log units. In native soleus, ΔpCa was only 0.40. Again, the effect of EMD 53998 on soleus–cTnI
(ΔpCa=0.56) more closely resembled the response found in cardiac muscle than that observed in native soleus muscle. The apparent
TnI-isoform dependence of the effects elicited by EMD 53998 suggests that its actions are modulated by the regulatory proteins
of the thin filament.
Received: 15 December 1997 / Accepted: 16 March 1998 相似文献
19.
20.
Rajesh Singh Pranav Gupta Praveen K. Sharma Edwin W. Ades Susan K. Hollingshead Shailesh Singh James W. Lillard 《Immunology》2014,141(4):514-530
Pneumococcal surface adhesin A (PsaA) is a multifunctional lipoprotein known to bind nasopharyngeal epithelial cells, and is significantly involved in bacterial adherence and virulence. Identification of PsaA peptides that optimally bind human leucocyte antigen (HLA) and elicit a potent immune response would be of great importance to vaccine development. However, this is hindered by the multitude of HLA polymorphisms in humans. To identify the conserved immunodominant epitopes, we used an experimental dataset of 28 PsaA synthetic peptides and in silico methods to predict specific peptide‐binding to HLA and murine MHC class II molecules. We also characterized spleen and cervical lymph node (CLN) ‐derived T helper (Th) lymphocyte cytokine responses to these peptides after Streptococcus pneumoniae strain EF3030 challenge in mice. Individual, yet overlapping, peptides 15 amino acids in length revealed residues of PsaA that consistently caused the highest interferon‐γ, interleukin‐2 (IL‐2), IL‐5 and IL‐17 responses and proliferation as well as moderate IL‐10 and IL‐4 responses by ex vivo re‐stimulated splenic and CLN CD4+ T cells isolated from S. pneumoniae strain EF3030‐challenged F1 (B6 × BALB/c) mice. In silico analysis revealed that peptides from PsaA may interact with a broad range of HLA‐DP, ‐DQ and ‐DR alleles, due in part to regions lacking β‐turns and asparagine endopeptidase sites. These data suggest that Th cell peptides (7, 19, 20, 22, 23 and 24) screened for secondary structures and MHC class II peptide‐binding affinities can elicit T helper cytokine and proliferative responses to PsaA peptides. 相似文献