Complement activation promotes colitis-associated carcinogenesis through activating intestinal IL-1ß/IL-17A axis.

Colitis-associated colorectal cancer (CAC) is the most serious complication of inflammatory bowel disease (IBD). Excessive complement activation has been shown to be involved in the pathogenesis of IBD. However, its role in the development of CAC is largely unknown. Here, using a CAC model induced by combined administration of azoxymethane (AOM) and dextran sulfate sodium (DSS), we demonstrated that complement activation was required for CAC pathogenesis. Deficiency in key components of complement (e.g., C3, C5, or C5a receptor) rendered tumor repression in mice subjected to AOM/DSS. Mechanistic investigation revealed that complement ablation dramatically reduced proinflammatory cytokine interleukin (IL)-1ß levels in the colonic tissues that was mainly produced by infiltrating neutrophils. IL-1ß promoted colon carcinogenesis by eliciting IL-17 response in intestinal myeloid cells. Furthermore, complement-activation product C5a represented a potent inducer for IL-1ß in neutrophil, accounting for downregulation of IL-1ß levels in the employed complement-deficient mice. Overall, our study proposes a protumorigenic role of complement in inflammation-related colorectal cancer and that the therapeutic strategies targeting complement may be beneficial for the treatment of CAC in clinic.

Behavioral changes of zebrafish according to cisplatin-induced toxicity of the balance system.

BACKGROUND AND OBJECTIVES: Zebrafish are commonly used as experimental animals in otolaryngology studies. However, the behavioral characteristics of these fish are not well known, especially those related to the vestibular system. The goal of this study was to evaluate behavioral changes in zebrafish due to toxicity in the balance system. MATERIALS AND METHODS: Zebrafish were exposed to 1000 µM cisplatin for 6 h. We, then, periodically monitored swimming depth, total swimming distance, peak swimming velocity, and mean swimming velocity of the fish for approximately 21 days. RESULTS: Total swimming distance (p < 0.0001), peak swimming velocity (p = 0.0063), and mean swimming velocity (p < 0.0001) in the cisplatin-administered group were significantly decreased when compared with control fish. CONCLUSION: Our findings demonstrate that cisplatin can alter the locomotion behavior of zebrafish.

Vestibular effects of lidocaine intratympanic injection in rats.

When lidocaine is locally delivered into the inner ear, it rapidly paralyzes the peripheral vestibular afferent neurons and induces unilateral vestibular loss. The goals of this study were to explore the possibility of developing intratympanic injection (IT) of lidocaine as a modality for treating acute vertigo. To evaluate the minimum concentration required, latent time, action duration, and possibility of lidocaine IT readministration to the vestibular system, we compared the development of horizontal nystagmus after IT of 2, 4, 6, 8, and 10% lidocaine solutions in rats. To identify the induction of vestibular compensation, c-Fos-like protein expression was observed in the vestibular nucleus. Results of our investigation showed that lidocaine IT concentrations greater than 4% induced vestibular hyporeflexia in the injected ear. In order to induce hyporeflexia 4 and 6% lidocaine solutions could also be repeatedly injected. Regardless of concentration, effects of the lidocaine IT dissipated gradually over time. Our findings could be used to develop novel methods for symptom control in vestibular disorder patients.

Neutrophil infiltration favors colitis-associated tumorigenesis by activating the interleukin-1 (IL-1)/IL-6 axis.

Neutrophil infiltration is a key event in chronic intestinal inflammation and associated colorectal cancer, but how these cells support cancer development is poorly understood. In this study, using a mouse model of colitis-associated cancer (CAC), we have demonstrated that infiltrated neutrophils produce large amounts of interleukin-1 (IL)-1ß that is critical for the development of CAC. Depletion of neutrophil or blockade of IL-1ß activity significantly reduced mucosal damage and tumor formation. This protumorigenic function of IL-1ß was mainly attributed to increased IL-6 secretion by intestine-resident mononuclear phagocytes (MPs). Furthermore, commensal flora-derived lipopolysaccharide (LPS) was identified to trigger IL-1ß expression in neutrophils. Importantly, accumulation of IL-1ß-expressing neutrophils was seen in lesions of patients suffering from ulceratic CAC and these infiltrated neutrophils induced IL-6 production by intestinal MPs in an IL-1ß-dependent manner. Overall, these findings reveal that in CAC milieu, infiltrating neutrophils secrete IL-1ß that promotes tumorigenesis by inducing IL-6 production by intestinal MPs.

Fabrication of ultrahigh density metal-cell-metal crossbar memory devices with only two cycles of lithography and dry-etch procedures.

A novel approach to the fabrication of metal-cell-metal trilayer memory devices was demonstrated by using only two cycles of lithography and dry-etch procedures. The fabricated ultrahigh density crossbar devices can be scaled down to ≤70 nm in half-pitch without alignment issues. Depending on the different dry-etch mechanisms in transferring high and low density nanopatterns, suitable dry-etch angles and methods are studied for the transfer of high density nanopatterns. Some novel process methods have also been developed to eliminate the sidewall and other conversion obstacles for obtaining high density of uniform metallic nanopatterns. With these methods, ultrahigh density trilayer crossbar devices (~2 × 10(10) bit cm(-2)-kilobit electronic memory), which are composed of built-in practical magnetoresistive nanocells, have been achieved. This scalable process that we have developed provides the relevant industries with a cheap means to commercially fabricate three-dimensional high density metal-cell-metal nanodevices.

A potential autocrine role for interferon tau in ovine trophectoderm.

Interferon tau (IFNT), a type I IFN produced by the conceptus trophectoderm, is the signal for maternal pregnancy recognition in ruminants. The purpose of this study was to investigate whether IFNT effected on the proliferation of ovine trophectoderm cells in an autocrine manner. Elongated ovine conceptuses (Days 15, Day 0 = day of mating) were collected for isolation of mononuclear ovine trophectoderm (oTr-1) cells, and conceptuses (Days 15 and 20, n = 4 and 3, respectively) were collected for RNA extraction. We demonstrated that the IFNT receptor, IFNAR1, was expressed in trophectoderm of day 15 and 20 conceptuses. Interestingly, the ovine trophectoderm cell line oTr-1 cultured in the presence of recombinant bovine IFNT (rbIFNT) displayed increased expressions of IFN-stimulated genes (ISGs), such as IFN-stimulated gene 15 (ISG15), 2-5-oligoadenylate synthetase 1 (OAS1) and bone marrow stromal cell antigen 2 (BST2). Meanwhile, the presence of rbIFNT in the culture media could promote the cell proliferation in a dose-dependent manner. Furthermore, the connective tissue growth factor, which has diverse functions in cell proliferation and is involved in conceptus elongation, was upregulated in oTr-1 cell by rbIFNT treatment in vitro. These data indicated that IFNT could act as an autocrine factor to regulate trophectoderm cell proliferation.

White matter tractography by diffusion tensor imaging plays an important role in prognosis estimation of acute lacunar infarctions.

The aim of this study was to evaluate the anatomical and clinical relationship between lacunar infarction and the corticospinal tract (CST) in patients with acute lacunar infarction and predict clinical outcome. We examined 28 pyramidal tract stroke patients in the acute phase or early subacute phase (<3 days) with a marked motor deficit. The anatomical location and the extent of CST involvement within the infarcts were visualized on three-dimensional colour-coded diffusion tensor tractography (DTT). With regard to the CST, all patients were divided into three clinical subgroups: Group 1 (intact type), Group 2 (partial involvement type) and Group 3 (whole involvement type). Subsequently, the severity of the motor deficit of each patient was determined according to the National Institutes of Health Stroke Scale (NIHSS) scores at the acute/early subacute phase (<3 days after onset of symptoms), early chronic phase (8-14 days) and outcome (30-60 days). NIHSS scores of Group 1 (12/28) were significantly lower than those of Group 2 (9/28) at the acute phase or early subacute phase (U = -2.816, p<0.01), and those of Group 2 were significantly lower than those of Group 3 (7/28) (U = -3.136, p<0.01). At outcome,NIHSS scores of Group 1 were significantly lower than those of Group 2 (U = -2.846, p<0.01), and scores of Group 2 were significantly lower than those of Group 3 (U = -3.130, p<0.01). At the same time, the NIHSS scores of each group gradually decreased from acute phase to outcome, Neurological improvement was statistically different among the three topographical types of infarction (H = 26.15, p<0.01; H = 11.03, p<0.01; H = 10.05, p<0.01). In conclusion, the three-dimensional colour-coded DTT allows in vivo differentiation of distinct CST stroke subtypes and may help in better establishing the prognosis for patients after CST stroke.

Differentiating among horse (Equus caballus), donkey (Equus asinus) and their hybrids with combined analysis of nuclear and mitochondrial gene polymorphism.

A novel and brief method of differentiating among horse (Equus caballus) and donkey (Equus asinus) and their hybrids (mule, E. asinus x E. caballus and hinny, E. caballus x E. asinus) with combined analysis of nuclear and mitochondrial gene polymorphism (CANMGP) was reported in the present report. A nuclear gene, protamine P1 gene of donkey was sequenced and compared with the known horse sequence from GenBank while a published equid mitochondrial gene, cytochrome b gene of donkey was compared with that of horse. In each of the two genes, a fixed nucleotide substitution within an exon that could be recognized by Dpn II restriction enzyme was found between the two species. Two pairs of primers were designed for amplifying the fragments within the two genes containing the informative nucleotide positions in 65 horses and 41 donkeys and 38 hybrids and conditions of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis were optimized. Horse, donkey and mule and hinny had their own specific cleavage patterns after the PCR-RFLP analysis was performed, which made it very easy to identify them from each other. As multiplex PCR can be conducted with the two pairs of primers and only one restriction enzyme is involved in PCR-RFLP analysis, the method described in the present study is a convenient way to identify horse and donkey and their hybrids. The idea involved in the method of CANMGP can be also used to differentiate other animal species or breeds and their hybrids.

Head tilt suppression test as a differential diagnostic tool in vertiginous patients.

The head tilt suppression test has been known to be a diagnostic tool to distinguish between centrally originating dizziness and peripheral vertigo, as the latter enhances the natural spontaneous firing rate of the velocity storage system and decreases the time constant; however, the otolith organ is now considered to be a cause of head tilting effect. Therefore we questioned whether the head tilt suppression test is still worth differential diagnostic tool. We measured the time constant and initial eye velocity of pre- and post-rotatory nystagmus in a velocity step test in nine healthy adults. The time constant was significantly affected by head tilting (p = 0.001), pre- and post-rotatory nystagmus (p = 0.020) and the compounding interaction between them (p < 0.000). The initial eye velocity was also significantly affected by pre- and post-rotatory nystagmus (p = 0.016) and the compounding interaction (p < 0.000), but not by head tilting (Wilks' Lambda = 0.054). The head tilt suppression test is a useful method for the differential diagnosis of vertiginous patients. It is affected by pre- and post-rotatory nystagmus and their interaction, however, other central parameters in vestibular function testing should also be considered in order to obtain an exact differential diagnosis.

Malignant triton tumor of the nasal cavity.

BACKGROUND: Malignant triton tumor is usually an aggressive sarcoma consisting of a malignant schwannoma with rhabdomyoblastic differentiation. However, malignant triton tumor of the nasal cavity is very rare. METHODS: A case report of a 38-year-old woman with polypoid mass, which bled easily in the right nasal cavity, and nasal obstruction is presented with a review of the literature pertaining to this unusual case. RESULTS: The malignant triton tumor was treated with wide surgical excision followed by radiation therapy. Histopathological diagnosis of the malignant triton tumor was made on the surgical specimen. The patient's postoperative course was unremarkable, and follow-up at 5 years reveals no evidence of disease. CONCLUSIONS: A malignant triton tumor in the nasal cavity is a rare disease. Head and neck surgeons should recognize the possibility of malignant triton tumor occurring in the nasal cavity.

[Role of paraventricular nucleus in natriuresis and diuresis induced by volume expansion in rabbits].

In sham-lesioned and paraventricular nucleus (PVN) lesioned rabbits, the peak increases of urine volume (UV) induced by volume expansion (VE) were 0.59+/-0.09 and 0.31+/-0.03 ml/min (P<0.01) respectively, whereas the peak increases of U(Na)V were respectively 66.76+/-6.74 and 36.05+/-3.44 micromol/min (P<0.01). No significant differences were found in the two increases induced by VE between rabbits with intact and those with sham-lesioned PVN. In rabbits with vagotomy there were no changes in the two increases after PVN lesion (P>0.05). In rabbits with renal denervation there was no significant change in natriuretic response after PVN lesion (P>0.05), but lesion of PVN significantly attenuated diuretic response (P<0.02). There were no significant differences in glomerular filtration rate (GFR) and renal plasma flow (RPF) before or after VE between the rabbits with intact and lesioned PVN (P>0.05). These results suggest that PVN is involved in the regulation of natriuresis and diuresis induced by VE, which are mediated by vagal afferent nerve, whereas the renal sympathetic efferent nerve may be involved in natriuretic response.

Expression of MXI1, a Myc antagonist, is regulated by Sp1 and AP2.

MXI1, a member of the MAD family of Myc antagonists, encodes a transcription factor whose expression must be tightly regulated to maintain normal cell growth and differentiation. To more closely investigate the transcriptional regulation of the human MXI1 gene, we have cloned and characterized the MXI1 promoter. After clarification of the 5'- and 3'-untranslated regions of the cDNA (indicating that the true length of the MXI1 transcript is 2643 base pairs), we identified two transcription initiation sites. We subsequently isolated the MXI1 promoter, which is GC-rich and lacks a TATA box. Although it contains at least six potential initiator sequences, functional studies indicate the proximal two initiator sequences in combination with nearby Sp1 and MED-1 sites together account for virtually all promoter activity. We also demonstrate that MXI1 promoter activity is repressed by high levels of AP2. These studies provide further insight into the complex regulatory mechanisms governing MXI1 gene expression and its role in cellular differentiation and tumor suppression.

[Role of spinal alpha adrenoceptor in the inhibition of renal sympathetic nerve activity and natriuresis induced by blood volume expansion in rabbits].

The effect of spinal alpha adrenoceptor blockage on the inhibition of renal sympathetic nerve activity (RSNA) and natriuresis induced by blood volume expansion was investigated in anesthetized and bilateral sinoaortic denervated rabbits. In the groups of rabbits with intrathecal injection of alpha-adrenoceptor blocker phentolamine or artificial cerebrospinal fluid the inhibition of RSNA induced by blood volume expansion were (-25.4 +/- 5.4)% and (-42.5 +/- 5.2)% respectively (P < 0.05). In the groups of rabbits with intrathecal injection of alpha 1 adtenoceptor blocker prazosin or artificial cerebrospinal fluid the inhibition of RSNA induced by blood volume expansion were (-29.3 +/- 6.1)% and (-42.5 +/- 5.2)% respectively (P < 0.05). These results suggested that both spinal alpha and alpha 1 adrenceptor blockage with attenuated the inhibition of RSNA induced by blood volume expansion. The spinal alpha 1 adrenceptor blockage with intrathecal injection of prazosin also attenuated signiticantly the natriuresis and diuresis induced by blood volume expansion (P < 0.05).

[Role of brain cholinergic system on diuresis and natriuresis induced by volume expansion in rats].

The role of brain cholinergic system on diuresis and natriuresis induced by volume expansion was studied in conscious rats. In a series of experiments, the diuretic, natriuretic and kaliuretic responses induced by volume expansion were compared in three groups of conscious rats pretreated respectively with intracerebroventricular (icv) injection of artificial cerebrospinal fluid (ACSF), atropine and hexamethonium. The natriuretic, kaliuretic and diuretic responses induced by volume expansion were much less in the animals with icv injection of atropine than in the control group with injection of ACSF (P less than 0.01). While the group pretreated with icv injection of hexamethonium showed no significant decrease in these responses of volume expansion than that of the control (P greater than 0.05). Volume expansion produced no change in insulin and PAH clearance in both the atropine and the ACSF group. Thus the atropine suppressed diuresis, natriuresis and kaliuresis are independent of changes in GFR and RPF. It is inferred from the results of the present investigation that volume expansion induced diuresis and natriuresis appear to be due to inhibition of water and sodium reabsorption in the renal tubules and regulated by certain brain cholinergic system.

[Studies on the stability and some other important physical properties of polysaccharides polyphase liposome (PPL)].

The stability and some other important physical properties of PPL were investigated by means of electron microscopy and MPV-TAS experiments. The results are rated as follows: Good integrity of liposome homogeneity of its particle size were reached, and at 100 degrees C PPL was found to undergo sterilization without causing changes of its shape and encapsulation efficiency for 1 h. Also, the distribution of PPL particle size and the regularity of the change of PPL particle in size were determined by Coulter counter. Using this method, the kinetic equation of coalescence of polyphase liposome and the activation energy for coalescence were obtained, and through these results the stability of PPL is elucidated.