T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

Nasal mucosal expression of nitric oxide synthases in patients with allergic rhinitis and its relation to asthma.

BACKGROUND: Nitric oxide (NO) has contradictory roles in the pathophysiology of allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large amounts produced by inducible NOS (iNOS) are proinflammatory. OBJECTIVE: To investigate the difference in constitutive endothelial NOS (eNOS) and iNOS expression in nonallergic and allergic mucosa and the possible relation of this to the coexistence of asthma in seasonal AR. METHODS: Seventeen patients (10 women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy specimens were obtained in all. Levels of eNOS and iNOS expressed as immunohistochemical scores (HSCOREs) were determined immunohistochemically from the specimens. RESULTS: The mean +/- SD HSCOREs for eNOS in patients with seasonal AR were not significantly different from those of the nonallergic controls (1.85 +/- 0.78 vs 1.63 +/- 0.54; P = .12). On the other hand, the mean +/- SD HSCOREs for iNOS were significantly higher in patients with seasonal AR (1.75 +/- 0.75 vs 0.71 +/- 0.6; P = .004). Furthermore, although eNOS expression was not different between seasonal AR patients with and without asthma, the mean +/- SD HSCOREs for iNOS were significantly higher in the patients with asthma (1.93 +/- 0.78 vs 1.65 +/- 0.55; P = .01). CONCLUSION: Increased expression of iNOS might have a role in the development of allergic inflammation in upper and lower airways and in comorbidity of AR and asthma.     

The influence of bilateral sagittal split ramus osteotomy on submental‐cervical aesthetics

The effect of orthodontic‐surgical treatment on submental‐cervical region was evaluated in a very limited number of studies. The aim of this study was to evaluate submental‐cervical soft tissue contour changes following mandibular advancement and set‐back procedures via bilateral sagittal split ramus osteotomy. Sixty‐seven patients were included in this study. Group 1 consisted of 27 skeletal Class II patients who underwent mandibular advancement surgery, whereas Group 2 consisted of 40 skeletal Class III patients who underwent mandibular set‐back surgery. Various linear and angular measurements were performed on pre‐operative and sixth month post‐operative cephalometric radiographs. A new method was used to evaluate the amount of sagging at submental region. The submental length did not change in Group 1; however, it decreased significantly in Group 2 (P < 0·05). The angle between submental plane and facial plane decreased to 95·9° from 98·8° in Group 1(P < 0·05), whereas it increased to 93·1° from 88·2° in Group2 (P < 0·05). The change of submental soft tissue sag was almost stable in Group 1, while 0·34 mm increase of sag was observed in Group 2. This increase was not statistically significant (P > 0·05). Mandibular set‐back and advancement procedures do not remarkably change the submental sag following approximately 6 mm jaw movement. Although mandibular advancement did not significantly effect submental length, soft tissue followed mandibular set‐back with a ratio of 1:1 at C‐point to projection of soft tissue pogonion and 1:0·7 at C‐point to soft tissue menton distances.     

Impact of Aortic Cross-Clamping Time on Peripheral Nerves: Experimental Model

Purpose: The present study investigated the correlation between extend aortic cross-clamping time and peripheral nerve injury on rats.Methods: 24 male, Sprague Dawley rats were divided into 3 groups; (a) control group: abdomen was directly closed after reached aorta, and followed by 72 hours, (b) short-term ischaemia-reperfusion group: peripheral nerve ischemia was induced in rats by supraceliac aortic occlusion for 20 min followed by 72 h of reperfusion, (c) long-term ischaemia-reperfusion group: peripheral nerve ischemia was induced for 30 min followed by 72 h of reperfusion. Preoperative and postoperative, electromyography (EMG) recordings were done. End of 72 h, the sciatic nerves were harvested from each animal for histopathological and biochemical analysis.Results: The mean compound muscle action potential (CMAP) amplitude of long-term ischaemia-reperfusion group was statically significant reduced when compared to the control group (p <0.01). However, the mean distal latency value of long-term ischaemia-reperfusion group was statically significant increased (p <0.01). On the other hand, there were statically significant differences between the results of malondialdehyde, edema and ischemia fiber degeneration grades on control and long-term ischaemia-reperfusion group (p <0.001).Conclusion: This study demonstrated that the extending cross clamping time directly harms the peripheral nerve of rats.     

Fatty liver-induced changes in stereotypic behavior in rats and effects of glucagon-like peptide-1 analog on stereotypy

Although understanding the relation between psychotic behavior and immune abnormalities has been the focus of research for many years, it remains to be elucidated whether the changes in cytokine levels are part of etiology or a result of the stress associated with the disorder. In accordance with previous studies on changes in cytokine levels due to metabolic changes and psychosis, we hypothesized that fatty liver may potentiate apomorphine-induced stereotypy in a rodent model and that a synthetic glucagon-like peptide-1 analog exenatide would ameliorate this effect. In this study, 18 male Sprague Dawley albino mature rats were used. We induced hepatosteatosis in these rats by feeding them with 30% fructose dissolved in drinking water for 8 weeks. The animals were divided into three groups, namely, the normal group, the intracerebroventricular (ICV) exenatide group, and the ICV NaCl group. Apomorphine-induced stereotypic behavior test was performed in all groups and the liver was removed for histopathological examination after all the rats were euthanized. In the nonalcoholic fatty liver (NAFL) group, stereotypy scores were significantly increased compared with the control group rats (p < 0.00001). A significant decrease in stereotypy scores were observed in the ICV exenatide group with NAFL when compared with the ICV saline group with NAFL (p < 0.005). In addition, brain malondialdehyde and tumor necrosis factor-α levels decreased in the ICV exenatide group. The results of this study showed that fatty liver enhances the effect of apomorphine on stereotypy, which was reversed by exenatide possibly by antioxidant and anti-inflammatory effects.     

Discovery and structure–activity relationship of plastoquinone analogs as anticancer agents against chronic myelogenous leukemia cells

Two series of amino‐1,4‐benzoquinones ( AQ1–18 ) based on the structural analogs of plastoquinones were synthesized and the structure–activity relationship against chronic myelogenous leukemia activity was examined. All of the synthesized compounds were tested for their cytotoxic effects on different leukemic cell lines. Of interest, AQ15 exhibited a better selectivity than the reference drug imatinib on cancer cells. Owing to this, AQ15 was selected for a further apoptosis/necrosis evaluation where AQ15 ‐treated K562 cells demonstrated similar apoptotic effects like imatinib‐treated cells at their IC₅₀ values. The inhibitory effects of AQ15 and the other three compounds with various activities against eight tyrosine kinases, including ABL1, were investigated. AQ15 showed weak activity against ABL1, and a correlation was observed between the anti‐K562 and anti‐ABL1 activities. The binding mode of AQ15 into the ATP binding pocket of ABL1 kinase was predicted in silico, showing the formation of some key interactions. In addition, AQ15 was shown to suppress the downstream signaling of BCR‐ABL in K562 cells. Finally, AQ15 obviously cleaved DNA in the presence of an iron(II) complex system, indicating that this can be the major mechanism of its antiproliferative action, whereas the mild inhibition of ABL kinase is just in‐part mechanism of its overall outstanding cellular activity.