EVOLUTION, Issue 2 2008
Max Reuter
Theory predicts that males adapt to sperm competition by increasing their investment in testis mass to transfer larger ejaculates. Experimental and comparative data support this prediction. Nevertheless, the relative importance of sperm competition in testis size evolution remains elusive, because experiments vary only sperm competition whereas comparative approaches confound it with other variables, in particular male mating rate. We addressed the relative importance of sperm competition and male mating rate by taking an experimental evolution approach. We subjected populations of Drosophila melanogaster to sex ratios of 1:1, 4:1, and 10:1 (female:male). Female bias decreased sperm competition but increased male mating rate and sperm depletion. After 28 generations of evolution, males from the 10:1 treatment had larger testes than males from other treatments. Thus, testis size evolved in response to mating rate and sperm depletion, not sperm competition. Furthermore, our experiment demonstrated that drift associated with sex ratio distortion limits adaptation; testis size only evolved in populations in which the effect of sex ratio bias on the effective population size had been compensated by increasing the numerical size. We discuss these results with respect to reproductive evolution, genetic drift in natural and experimental populations, and consequences of natural sex ratio distortion. [source]

Metallic Taste: An Unusual Reaction to Botulinum Toxin A

DERMATOLOGIC SURGERY, Issue 5 2003
Christian Murray MD
BACKGROUND Botulinum neurotoxin formulations are safe and effective agents for the treatment of facial rhytides. OBJECTIVES A patient is described who complained of metallic taste after each treatment with botulinum toxin A (BTX-A). RESULTS The sensation of metallic taste diminished after successive treatments with BTX-A, despite adequate dosing for cosmetic purposes. CONCLUSION Metallic taste is associated with the use of numerous medications; however, the pathogenesis remains unclear. Alteration in zinc metabolism, which may occur with BTX-A administration, has been suggested as a possible mechanism. Although this is the first known report of dysgeusia after BTX-A, physicians and patients may be reassured that the taste alteration was self-limited and was not significantly problematic for the patient in our case. [source]

The nervous system and gastrointestinal function

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2008
Muhammad A. Altaf
Abstract The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia, feeding intolerance, gastroesophageal reflux, abdominal pain, and constipation are few of the medical problems frequently encountered in children with developmental disabilities. Alteration in bowel motility have been described in most of these disorders and can results from a primary defect in the enteric neurons or central modulation. The development and physiology of the enteric nervous system is discussed along with the basic mechanisms involved in controlling various functions of the gastrointestinal tract. The intestinal motility, neurogastric reflexes, and brain perception of visceral hyperalgesia are also discussed. This will help better understand the pathophysiology of these disorders in children with developmental disabilities. © 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:87,95. [source]

Alteration of proteins expression in apoptotic FL cells induced by MCLR

ENVIRONMENTAL TOXICOLOGY, Issue 4 2008
Ming-Luan Xing
Abstract Microcystins (MCs) are a family of monocyclic heptapeptide hepatotoxins produced by freshwater species of cyanobacteria. Microcystin-LR (MCLR) is the most frequently studied and most toxic in over 80 MC congeners. Great deals of studies have demonstrated that MCLR can induce apoptosis in a wide variety of cell types. Although much evidence indicates that mitochondria play a pivotal role in MCLR-induced apoptosis, the complicated apoptosis mechanisms induced by MCLR have not been completely characterized. It is possible that there are other apoptotic pathways existing in MCLR-induced apoptosis. The present study was undertaken to determine the expression of PP2A, CHOP, Bax, Bcl-2, and p53 proteins in MCLR-induced apoptosis in FL cells. The results showed that MCLR could induce apoptosis in FL cells and the process was accompanied with the upregulation of PP2A, Bax, and p53 proteins and the downregulation of Bcl-2 proteins. In addition, the CHOP protein was upregulated at most treatment groups and decreased at the highest concentration group. These results, especially the alteration of PP2A and CHOP proteins might provide new insights into MCLR-induced apoptosis. © 2008 Wiley Periodicals, Inc. Environ Toxicol 2008. [source]

Alteration of normal cellular profiles in the scleractinian coral (Pocillopora damicornis) following laboratory exposure to fuel oil

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2006
Luc Rougée
Abstract Petroleum contamination from oil spills is a continuing threat to our ocean's fragile ecosystems. Herein, we explored the effects of the water-soluble fraction of crude oil on a stony coral, Pocillopora damicornis (Linneaeus 1758). We developed methods for exposing corals to various concentrations of crude oil and for assessing the potential molecular responses of the corals. Corals were exposed to water-accommodated fraction solutions, and appropriate cellular biomarkers were quantified. When compared to the "healthy" control specimens, exposed corals exhibited shifts in biomarker concentrations that were indicative of a shift from homeostasis. Significant changes were seen in cytochrome P450 1-class, cytochrome P450 2-class, glutathione- S -transferase-pi, and cnidarian multixenobiotic resistance protein-1 biomarkers, which are involved the cellular response to, and manipulation and excretion of, toxic compounds, including polycyclic aromatic hydrocarbons. A shift in biomarkers necessary for porphyrin production (e.g., protoporphyrinogen oxidase IX and ferrochelatase) and porphyrin destruction (e.g., heme oxygenase-1 and invertebrate neuroglobin homologue) illustrates only one of the cellular protective mechanisms. The response to oxidative stress was evaluated through measurements of copper/zinc superoxide dismutase-1 and DNA glycosylase MutY homologue-1 concentrations. Likewise, changes in heat shock protein 70 and small heat shock proteins indicated an adjustment in the cellular production of proteins. Finally, the results of this laboratory study were nearly identical to what we observed previously among corals of a different species, Porites lobata, exposed to an oil spill in the field after the grounding of the Merchant Vessel Kyowa Violet. [source]

Abnormal Excitability of Hippocampal CA3 Neurons in Noda Epileptic Rat (NER): Alteration of Seizure with Aging

EPILEPSIA, Issue 2000
Ryosuke Hanaya
Purpose: Noda epileptic rat (NER), a mutant found in thc colony of Crj:Wistar rats, spontaneously shows tonic-clonic convulsions approximately once every 30 hours from 8,16 weeks of age. A long-lasting dcpolarization shift accompanied by repetitivc firings are observed in hippocampal CA3 pyramidal neurons of NER with seizures. Using hippocampal slice preparations of NER, the present electrophysiologi- cal study was performed to elucidate whether this abnormal firing in CA3 neurons developed with age and if abnormality of Ca2+ channel was involved. Methods: Hippocampal slices (40Opm) werc prepared from NER and normal Wistar rats (age; 4,29 weeks). A single rectangular pulse stimulus composed of 0.1-ms duration was delivered to the mossy fibers every 5 seconds though a bipolar electrode placed in the granular cell layer of the dentate gyrus. Intracellular recording was made from the CA3 pyramidal cell using a microelectrode containing 3M KCI intracellular recordings. A Ca2+ spike was elicited by applying a depolarizing pulse (InA, 120ms) in the cell through the recording electrode under a blockadc of Na+ and K+ channels using 1 pM tetrodotoxin and I 0mM tctraethylammonium added to the artificial CSF, respectivcly. Nicardipine (I-IOOnM), a Ca2+ channel blocker, was applicd to the bath. Results: Thirty-seven slices from I9 NER and 6 slices from 4 normal Wishe rats were used. There were no obvious changes in the resting membrane potentials of CA3 neurons between NER and Wistar rats tested. When a single stimulus was delivered to the mossy fibers, a long-lasting depolarization shift accompanied by repetitive firings followed by after-hyperpolarization werc also obtained i n hippocampal CA3 neurons of young NER (4,5 weeks of age) before occurrence of any seizurcs, although the depolarization shift in younger NER was shorter than that in NER aged more than 6 weeks. These abnormal firings werc evokcd in 58% and 30% of all CA3 neurons tested in the younger and mature NER (6,1 5 weeks of age), respectively. Furthermore, abnormal firing was not elicited in NER aged after I6 weeks. Agc-matched Wistar rats showed only single action potentials without any depolarization shift with single mossy fiber stimulation. Bath application of nicardipine (IOnM) inhibited this long-lasting depolarization shift and the accompanying repetitive firing followed by afterhypcrpolarization without affecting the first spike induced by mossy fiber stimulations. Furthermore, nicai-dipine (IOnM) inhibited the Ca2+ spikes elicited by applying a depolarizing pulse in the neurons of NER with seizures, although a higher dose (100nM) did not affect those in Wistar rats. Conclusions: These findings indicate that abnormal excitability of the NER CA3 pyramidal neurons is probably due to abnormality in the Ca2+ channcls. The abnorinal excitability was observed in NER at an age when tonic-clonic convulsions were not detected, suggesting that thc hippocampus may probably scrve as an epileptogenic focus in younger NER and the seizure impulses originating i n this area are transinittcd to the new other seizurc foci in mature NER. [source]

Effects of angiogenic regulators on in vitro proliferation and cytokine secretion by native human acute myelogenous leukemia blasts

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2003
Øystein Bruserud
Abstract: Angiogenesis seems to be important in the pathogenesis of acute myelogenous leukemia (AML). The endothelial cell proliferation and microvessel formation are regulated by a wide range of soluble mediators, including angiogenin, angiopoietin-2, basic fibroblast growth factors, vascular endothelial growth factor (VEGF), VEGF-D, angiostatin and endostatin. In the present study, it has been investigated whether these mediators have an additional direct effect on the proliferation and cytokine release by native human AML blasts. AML cells derived from a large group of consecutive patients were investigated. All these mediators could alter the proliferation and cytokine release [interleukin (IL) 1,, IL6, IL8, tumor necrosis factor ,] for a minority of patients. Alteration of spontaneous proliferation by at least one mediator was detected in five of 38 patients; whereas, altered cytokine (Flt3-ligand, granulocyte-macrophage colony-stimulating factor, stem cell factor)-dependant proliferation was observed for 10 patients. Growth enhancement was most frequently observed, whereas growth inhibition was uncommon. The effects on AML blast proliferation were often dependant on or were modulated by the presence of the three hematopoietic growth factors. Based on the present results, it is concluded that angioregulatory mediators have additional growth-enhancing effects directly on the AML blasts for certain patients. However, based on the results from this investigation and previous studies it is suggested that their major contribution to the pathogenesis of AML is through their effects on regulation of bone marrow angiogenesis, and future studies of these mediators in AML should probably focus on these effects. [source]

AgC10, a mucin from Trypanosoma cruzi, destabilizes TNF and cyclooxygenase-2 mRNA by inhibiting mitogen-activated protein kinase p38

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2004
Pilar Alcaide
Abstract Secretion of proinflammatory mediators by activated macrophages plays an important role in the immune response to Trypanosoma cruzi. We have previously reported that AgC10, a glycosylphosphatidylinositol-anchored mucin from T. cruzi, inhibits TNF secretion by activated macrophages (de Diego, J., Punzon, C., Duarte, M. and Fresno, M., Alteration of macrophage function bya Trypanosoma cruzi membrane mucin. J. Immunol. 1997. 159: 4983,4989). In this report we have further investigated the molecular mechanisms underlying this inhibition. AgC10 inhibited TNF, IL-10 and cyclooxygenase-2 (COX-2) synthesis by macrophages activated with LPS or LPS plus IFN-, in a dose-dependent manner. AgC10 did not affect other aspects of macrophage activation induced by LPS, such as inducible nitric oxide synthase (iNOS) expression. AgC10 also had no effect on TNF or COX-2 transcription or the induction of their promoters but inhibited the stability of TNF and COX-2 mRNA, which are regulated post-transcriptionally by the mitogen-activated protein kinase (MAPK) p38 pathway. AgC10 was found to inhibit both the activation and the activity of p38 MAPK, since MAPK activated protein kinase-2 (MAPKAP-K2 or MK-2) phosphorylation was also strongly inhibited. This led to TNF and COX-2 mRNA destabilization. In contrast, AgC10 did not affect p38 activation induced by TNF. Furthermore, AgC10 inhibition must lie upstream in the MAPK activation pathway by LPS, since this mucin also inhibited extracellularly regulated kinase (ERK) and Jun kinase (JNK)activation. [source]

Altered fatty acid pattern of phospholipids and triglycerides in the submandibular gland of ,3-depleted rats

EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2007
Christine Delporte
Alteration of the phospholipid (PL) and triglyceride (TG) fatty acid pattern was recently documented in several organs of rats depleted in long-chain polyunsaturated ,3 fatty acid (,3 rats). This study extends such a knowledge to the submandibular gland. The total PL and TG content of the salivary gland was not different in control and ,3 rats. The sole ,3 fatty acids found in ,3 rats (C22:5,3 and C22:6,3) were present at levels 3,12 times lower than in control rats. The C22:5,3/C22:6,3 ratio was increased threefold in ,3 rats. The PL and TG C16:0/C16:1,7 and C18:0/C18:1,9 ratios were decreased in ,3 rats. The conversion of C18:2,6 to C20:4,6 and C22:4,6 appeared facilitated in the ,3 rats. Some of these rats were injected intravenously, 60,120 min before killing, with either a medium-chain triglyceride:fish oil emulsion or a control medium-chain triglyceride:olive oil emulsion. The former emulsion increased the PL C22:5,3 and C22:6,3 content and prevented the age-related decrease in C16:0/C16:1,7 and C18:0/C18:1,9 ratios otherwise also recorded in PL. In conclusion, these findings document an increased activity of ,9-desaturase, a more efficient conversion of C18:2,6 to its metabolites, and an impaired generation of C22:6,3 from C22:5,3 in ,3 rats. [source]

Alteration in regulation of inflammatory response to influenza a virus and endotoxin in suckling rat pups: a potential relationship to sudden infant death syndrome

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2004
Jane Blood-Siegfried
Abstract Data increasingly implicate a possible role of immune and inflammatory responses to infection in sudden infant death syndrome (SIDS). We have previously described a dual challenge model that results in pathology, organ damage, vascular collapse and unexplained death similar to that seen in SIDS. In this study, we examined changes in inflammatory cytokine mRNA in the lung and liver and regulation of pathways associated with nitric oxide production. Our data suggest that priming of the immune system by mild viral infection disturbs normal inflammatory response to endotoxin. This results in an increased nitric oxide synthase production, most likely the cause of liver pathology and clotting abnormalities. [source]

Alteration of enhancer of polycomb 1 at 10p11.2 is one of the genetic events leading to development of adult T-cell leukemia/lymphoma

GENES, CHROMOSOMES AND CANCER, Issue 9 2009
Shingo Nakahata
Adult T-cell leukemia/lymphoma (ATLL) is a malignant tumor caused by latent human T-lymphotropic virus 1 (HTLV-1) infection. We previously identified a common breakpoint cluster region at 10p11.2 in acute-type ATLL by spectral karyotyping. Single nucleotide polymorphism array comparative genomic hybridization analysis of the breakpoint region in three ATLL-related cell lines and four patient samples revealed that the chromosomal breakpoints are localized within the enhancer of polycomb 1 (EPC1) gene locus in an ATLL-derived cell line (SO4) and in one patient with acute-type ATLL. EPC1 is a human homologue of the E(Pc) enhancer of polycomb gene of Drosophila. Inappropriate expression of the polycomb group gene family has been linked to the loss of normal gene silencing pathways, which can contribute to the loss of cell identity and malignant transformation in many kinds of cancers. In the case of the SO4 cell line, which carried a der(10)t(2;10)(p23;p11.2) translocation, EPC1 was fused with the additional sex combs-like 2 (ASXL2) gene at 2p23.3 (EPC1/ASXL2). In the case with an acute-type ATLL, who carried a der(10)del(10)(p11.2)del(10)(q22q24) translocation, a putative truncated EPC1 gene (EPC1tr) was identified. Overexpression of EPC1/ASXL2 enhanced cell growth in T-leukemia cells, and a GAL4-EPC1/ASXL2 fusion protein showed high transcriptional activity. Although a GAL4-EPC1tr fusion protein did not activate transcription, overexpression of EPC1tr accelerated cell growth in leukemia cells, suggesting that the EPC1 structural abnormalities in the SO4 cell line and in the patient with acute-type ATLL may contribute to leukemogenesis. © 2009 Wiley-Liss, Inc. [source]

Alteration of the food web along the Antarctic Peninsula in response to a regional warming trend

GLOBAL CHANGE BIOLOGY, Issue 12 2004
Mark A. Moline
Abstract In the nearshore coastal waters along the Antarctic Peninsula, a recurrent shift in phytoplankton community structure, from diatoms to cryptophytes, has been documented. The shift was observed in consecutive years (1991,1996) during the austral summer and was correlated in time and space with glacial melt-water runoff and reduced surface water salinities. Elevated temperatures along the Peninsula will increase the extent of coastal melt-water zones and the seasonal prevalence of cryptophytes. This is significant because a change from diatoms to cryptophytes represents a marked shift in the size distribution of the phytoplankton community, which will, in turn, impact the zooplankton assemblage. Cryptophytes, because of their small size, are not grazed efficiently by Antarctic krill, a keystone species in the food web. An increase in the abundance and relative proportion of cryptophytes in coastal waters along the Peninsula will likely cause a shift in the spatial distribution of krill and may allow also for the rapid asexual proliferation of carbon poor gelatinous zooplankton, salps in particular. This scenario may account for the reported increase in the frequency of occurrence and abundance of large swarms of salps within the region. Salps are not a preferred food source for organisms that occupy higher trophic levels in the food web, specifically penguins and seals, and thus negative feedbacks to the ecology of these consumers can be anticipated as a consequence of shifts in phytoplankton community composition. [source]

Alteration in Nature of Cluster Headache During Subcutaneous Administration of Sumatriptan

HEADACHE, Issue 1 2000
Rachel Hering-Hanit MD
Objectives., To document the relationship between the 5-HT receptor agonist sumatriptan and a change in the nature of cluster headache in four cases. To relate the findings to the literature on the use of sumatriptan in both cluster headache and migraine. Background., Studies of the efficacy and adverse effects of long-term treatment with sumatriptan in cluster headache are limited and report conflicting findings. Methods., Four cases are described. Results., All four patients developed a marked increase in the frequency of attacks 3 to 4 weeks after initiating treatment with the drug for the first time. Three patients also developed a change in headache character, and 2 experienced prolongation of the cluster headache period. Withdrawal of the drug reduced the frequency of headaches and eliminated the newly developed type of headache. Conclusions., Determination of the effects of long-term use of sumatriptan will result in more precise guidelines for the frequency and duration of treatment with this otherwise extremely beneficial drug. [source]

Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis

HISTOPATHOLOGY, Issue 6 2010
Maria S Tretiakova
Tretiakova M S, Shabani-Rad M T, Guggisberg K, Hart J, Anders R A & Gao Z-h (2010) Histopathology,56, 683,693 Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis Aims:, To compare the expression of genes involved in p53, Wnt/,-catenin, and retinoblastoma (Rb) 1 pathways between cirrhosis-associated hepatocellular carcinoma (HCC-C) and hepatocellular carcinoma arising in non-cirrhotic liver (HCC-NC). Methods and results:, The gene expression profile was analysed using oligo-DNA arrays, and then validated at protein level in a tissue microarray using immunohistochemistry. Compared with their background non-neoplastic liver tissue, HCC-C showed a significantly higher rate of p53, ,-catenin (protein only) and cyclin D1 expression, whereas HCC-NC showed a significantly higher rate of p21Waf1/cip1 and p27Kip1 expression. HCC-C had a significantly higher rate of p53 expression and a significantly lower rate of p21waf1/cip1 expression than HCC-NC. There was no statistically significant association between the expression of genetic markers and tumour histological grade, underlying aetiology, or lymphovascular invasion. Aberrant ,-catenin expression was more commonly seen in single tumours in comparison with multiple tumours. Increased p16INK4 and p21waf1/cip1 expression was more commonly observed in large-sized tumours (>50 mm) than small-sized tumours. Conclusions:, Alteration of the p53 pathway plays a more important role in the pathogenesis of HCC-C, whereas alterations in cell cycle regulators p21waf1/cip1 and p27Kip1 play a more important role in the pathogenesis of HCC-NC. [source]

Alteration of ,-catenin localization in salivary pleomorphic adenomas is not related to t(3;8)(p21;q12) and is mainly present in non-epithelial cell types

HISTOPATHOLOGY, Issue 2 2008
I Fonseca
First page of article [source]

Alteration of CXCR4 expression and Th1/Th2 balance of peripheral CD4-positive T cells can be a biomarker for leukocytapheresis therapy for patients with refractory ulcerative colitis

INFLAMMATORY BOWEL DISEASES, Issue 7 2009
Hiroshi Nakase MD
No abstract is available for this article. [source]

An in vitro comparison of canal preparation using two automated rotary nickel,titanium instrumentation techniques

INTERNATIONAL ENDODONTIC JOURNAL, Issue 4 2000
S. J. Jardine
Abstract Aim The aim of this study was to compare the efficacy of root canal preparation using two automated rotary nickel,titanium instrumentation techniques with a double flared balanced forces hand preparation technique, using stainless steel files in extracted human teeth. Methodology Sixty root canals in extracted human teeth were matched for curvature, length and diameter and divided evenly between three groups (group 1 = double flare using Flexofiles®, group 2 = rotary nickel,titanium using McXIM® instruments and group 3 = rotary nickel,titanium using Profile® .04 TaperTM Series 29 instruments). The instruments were used according to the manufacturer's instructions in a torque controlled motor and handpiece (groups 2 and 3) and according to a predetermined procedure in group 1. A standardized radiographic technique using mercury as a contrast medium was used to evaluate the canal shape before and after preparation in the plane of maximum curvature. The pre- and postoperative radiographic images were compared against each other and with a predicted ,ideal preparation' calculated from a projection of the final instrument dimensions. The outcome measures were changes in canal dimensions as quantified by measuring the changes in the position of the inner and outer wall at 1 mm intervals. Alteration in canal curvature could be inferred by comparison with the ideal preparation. Results The degree of canal curvature did not influence the effectiveness of any of the techniques. The results showed no statistically significant differences in the outcome measures between the groups (two-way anova). There were no significant differences in canal wall position changes at any level except the apical three, where significantly less change occurred in all groups (P = 1%). Instruments fractured in three canals, with acute curves in groups 2 and 3. Conclusions Canal curvatures were equally and well maintained following preparation in all the groups, as long as the instrument did not fracture. [source]

Involvement of Ca2+ and ROS in ,-tocopheryl succinate-induced mitochondrial permeabilization

INTERNATIONAL JOURNAL OF CANCER, Issue 8 2010
Vladimir Gogvadze
Abstract Release of mitochondrial proteins such as cytochrome c, AIF, Smac/Diablo etc., plays a crucial role in apoptosis induction. A redox-silent analog of vitamin E, ,-tocopheryl succinate (,-TOS), was shown to stimulate cytochrome c release via production of reactive oxygen species (ROS) and Bax-mediated permeabilization of the outer mitochondrial membrane. Here we show that ,-TOS facilitates mitochondrial permeability transition (MPT) in isolated rat liver mitochondria, Tet21N neuroblastoma cells and Jurkat T-lymphocytes. In particular, in addition to ROS production, ,-TOS stimulates rapid Ca2+ entry into the cells with subsequent accumulation of Ca2+ in mitochondria,a prerequisite step for MPT induction. Alteration of mitochondrial Ca2+ buffering capacity was observed as early as 8 hr after incubation with ,-TOS, when no activation of Bax was yet detected. Ca2+ accumulation in mitochondria was important for apoptosis progression, since inhibition of mitochondrial Ca2+ uptake significantly mitigated the apoptotic response. Importantly, Ca2+ -induced mitochondrial destabilization might cooperate with Bax-mediated mitochondrial outer membrane permeabilization to induce cytochrome c release from mitochondria. [source]

Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

INTERNATIONAL JOURNAL OF CANCER, Issue 4 2006
Stephen O. Ikuerowo
Abstract Cyclin B1, identified as a regulator of late cell cycle, is involved in the development and progression of a variety of human malignancies. To clarify the role of cyclin B1 in the pathogenesis and prognosis of renal cell carcinoma (RCC), protein expression was compared with clinicopathological characteristics of patients as well as the long-term survival after surgical therapy. Expression analysis was carried out by immunohistochemistry and tissue microarray analysis. The microarrays that represented the primary tumors, their invasion front and normal peritumoral renal parenchyma contained 753 tissue cores obtained from 251 randomly selected nephrectomy specimens. Immunopositivity within the primary tumors was significantly associated with tumor stage (pT) (p < 0.01), lymph node status (pN) (p < 0.01) as well as the presence of systemic metastatic disease (p = 0.01). Subcellular expression in the cytoplasm of tumor cells significantly correlated with pT (p = 0.02) and pN (p = 0.03). When peritumoral tissue samples exhibited a relative amount of <10% of positively reacting epithelial cells, cyclin B positivity was identified to predict long-term survival of patients in univariate analysis (p < 0.01) whereas borderline significance was observed in multivariate statistical analysis (p = 0.05). Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with the tendency towards tumor progression, indicating the significant role of cyclin B1 in the development and pathogenesis of RCC. The result of uni- and multivariate statistical analysis suggests the prognostic value of cyclin B1 for RCC patients. © 2006 Wiley-Liss, Inc. [source]

Alteration of RANKL-Induced Osteoclastogenesis in Primary Cultured Osteoclasts From SERCA2+/, Mice,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2009
Yu-Mi Yang
Abstract RANKL is essential for the terminal differentiation of monocytes/marcrophages into osteoclasts. RANKL induces long-lasting oscillations in the intracellular concentration of Ca2+ ([Ca2+]i) only after 24 h of stimulation. These Ca2+ oscillations play a switch-on role in NFATc1 expression and osteoclast differentiation. Which Ca2+ transporting pathway is induced by RANKL to evoke the Ca2+ oscillations and its specific role in RANKL-mediated osteoclast differentiation is not known. This study examined the effect of a partial loss of sarco/endoplasmic reticulum Ca2+ ATPase type2 (SERCA2) on osteoclast differentiation in SERCA2 heterozygote mice (SERCA2+/,). The BMD in the tibias of SERCA2+/, mice increased >1.5-fold compared with wildtype mice (WT). RANKL-induced [Ca2+]i oscillations were generated 48 h after RANKL treatment in the WT mice but not in the SERCA2+/, bone marrow,derived macrophages (BMMs). Forty-eight hours after RANKL treatment, there was a lower level of NFATc1 protein expression and markedly reduced translocation of NFATc1 into the nucleus during osteoclastogenesis of the SERCA2+/, BMMs. In addition, RANKL treatment of SERCA2+/, BMMs incompletely induced formation of multinucleated cells, leading to reduced bone resorption activity. These results suggest that RANKL-mediated induction of SERCA2 plays a critical role in the RANKL-induced [Ca2+]i oscillations that are essential for osteoclastogenesis. [source]

Alteration and role of heat shock proteins in acute pancreatitis

JOURNAL OF DIGESTIVE DISEASES, Issue 5 2010
Jia Yan FENG
Many etiological factors are involved in the pathogenesis of acute pancreatitis. The pathogenesis of acute pancreatitis has been attributed to such causes as trypsin autodigestion, pancreatic microcirculation malfunction, the calcium overload in pancreatic acinar cells, oxygen free radical injury, cytokine injury, and has been treated in detail in numerous reviews. More recently, heat shock proteins (HSP), particularly heat shock protein 60 (HSP60), have receive increasing attention as another possible factor in the pathogenesis and development of acute pancreatitis. This brief review aims to: (i) outline our current understanding of HSP and their role in pancreatitis; (ii) discuss the available evidences that suggest HSP's interplay between pancreas tissues and etiological agents; (iii) delineate the functional mechanisms of HSP proposed by different research groups, and offer new thinking in preventing and treating acute pancreatitis in general. [source]

Enhancement of poly-adenosine diphosphate-ribosylation in human hepatocellular carcinoma

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2000
Fumio Nomura
Abstract Background: Poly-adenosine diphosphate (ADP)-ribosylation, catalysed by poly(ADP-ribose) polymerase (PARP), is a post-translational modification of nuclear proteins and is involved in a wide range of biological processes including DNA repair, cell proliferation and malignant transformation. Alteration of this reaction in human hepatocellular carcinoma (HCC) is of interest, but has not yet been explored. The aim of this study was to evaluate poly-ADP-ribosylation and to compare the expression of PARP in HCC and adjacent non-tumour tissues. Methods: Tumorous and adjacent non-tumorous tissues were obtained from five consecutive patients with HCC during surgery for tumour resection. Tissue homogenates were subjected to ADP-ribosylation with [32P]-nicotinamide adenine dinucleotide. The ADP-ribosylated proteins were separated by sodium dodecylsulfate,polyacrylamide gel electrophoresis, followed by autoradiography. Expression of PARP was also evaluated by western blotting. Results: Several proteins were ADP-ribosylated in human HCC tissues. Notably, the radiolabelling of a 116-kDa protein was remarkably greater than that in adjacent non-tumorous tissues (86.5 ± 35.2 arbitrary units by densitometry vs 12.2 ± 9.9, mean± SD, n = 5, P < 0.02). The radiolabelling of the 116-kDa protein was decreased in the presence of PARP inhibitors in a concentration-dependent manner. Immunoblot analyses revealed that the radiolabelled protein was PARP and that its expression was significantly greater in HCC than in adjacent non-tumorous tissues (333 ± 204% of non-tumorous tissue, P < 0.05). Conclusions: We found that poly-ADP-ribosylation and PARP expression were significantly increased in human HCC compared with those in adjacent non-tumorous tissues in surgically obtained specimens. [source]

Alteration of proton diffusivity associated with passive muscle extension and contraction

JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2008
Masamitsu Hatakenaka MD
Abstract Purpose To determine whether passive muscle extension and contraction affect the proton diffusivity of the muscle. Materials and Methods Five male subjects were examined. The fractional anisotropy (FA), and primary (,1), secondary (,2), and tertiary eigenvalues (,3) of the right tibialis anterior and medial gastrocnemius muscles were compared between conditions of passive plantar flexion and passive dorsiflexion of the ankle joint. Results In the tibialis anterior, FA, and ,1 at dorsiflexion decreased significantly (P < 0.01 and P < 0.01, respectively) compared to those at plantar flexion, but ,3 at dorsiflexion increased significantly (P = 0.02). In the gastrocnemius, FA and ,1 at dorsiflexion increased significantly (P < 0.01 and P < 0.01, respectively) compared to those at plantar flexion, but ,3 at dorsiflexion decreased significantly (P < 0.01). The ,2 value showed no significant change in either the tibialis anterior or medial gastrocnemius. Conclusion The results indicate that passive muscle extension and contraction associated with passive joint movement would affect the proton diffusivity of the muscle. This alteration of proton diffusivity is probably associated with microscopic structural changes of the muscle. J. Magn. Reson. Imaging 2008;27:932,937. © 2008 Wiley-Liss, Inc. [source]

Oxidative modulation of nuclear factor-,B in human cells expressing mutant fALS-typical superoxide dismutases

JOURNAL OF NEUROCHEMISTRY, Issue 5 2002
Arianna Casciati
Abstract Previous evidence supports the notion of a redox regulation of protein phosphatase calcineurin that might be relevant for neurodegenerative processes where an imbalance between generation and removal of reactive oxygen species occurs. We have recently observed that calcineurin activity is depressed in human neuroblastoma cells expressing Cu,Zn superoxide dismutase (SOD1) mutant G93A and in brain areas from G93A transgenic mice, and that mutant G93A-SOD1 oxidatively inactivates calcineurin in vitro. We have studied the possibility that, by interfering directly with calcineurin activity, mutant SOD1 can modulate pathways of signal transduction mediated by redox-sensitive transcription factors. In this paper, we report a calcineurin-dependent activation of nuclear factor-,B (NF-,B) induced by the expression of familial amyotrophic lateral sclerosis (fALS)-SOD1s in human neuroblastoma cell lines. Alteration of the phosphorylation state of I,B, (the inhibitor of NF-,B translocation into the nucleus) and induction of cyclooxygenase 2 are consistent with the up-regulation of this transcription factor in this system. All of these modifications might be relevant to signaling pathways involved in the pathogenesis of fALS. [source]

Alteration of amino acid metabolism in neuronal aggregate cultures exposed to hypoglycaemic conditions

JOURNAL OF NEUROCHEMISTRY, Issue 6 2002
Paul Honegger
Abstract The neuronal effects of glucose deficiency on amino acid metabolism was studied on three-dimensional cultures of rat telencephalon neurones. Transient (6 h) exposure of differentiated cultures to low glucose (0.25 mm instead of 25 mm) caused irreversible damage, as judged by the marked decrease in the activities of two neurone-specific enzymes and lactate dehydrogenase, 1 week after the hypoglycemic insult. Quantification of amino acids and ammonia in the culture media supernatants indicated increased amino acid utilization and ammonia production during glucose-deficiency. Measurement of intracellular amino acids showed decreased levels of alanine, glutamine, glutamate and GABA, while aspartate was increased. Added lactate (11 mm) during glucose deficiency largely prevented the changes in amino acid metabolism and ammonia production, and attenuated irreversible damage. Higher media levels of glutamine (4 mm instead of 0.25 mm) during glucose deprivation prevented the decrease of intracellular glutamate and GABA, while it further increased intracellular aspartate, ammonia production and neuronal damage. Both lactate and glutamine were readily oxidized in these neuronal cultures. The present results suggest that in neurones, glucose deficiency enhances amino acid deamination at the expense of transamination reactions. This results in increased ammonia production and neuronal damage. [source]

Alteration in Hypothalamic Neuropeptide Y (NPY) Secretion May Underlie Female Reproductive Ageing: Induction of Steroid-Induced Luteinising Hormone Surge by NPY in Ovariectomised Aged Rats

JOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006
A. Sahu
A large body of evidence suggests that a defect in the hypothalamic function may be the primary cause of reproductive ageing in female rats. We have previously shown that luteinising hormone (LH)-surge associated changes in hypothalamic neuropeptide Y (NPY) gene expression and median eminence (ME) NPY levels seen in young rats do not occur in middle-aged (MA) rats. The present study examined whether hypothalamic NPY release is altered during the steroid-induced LH surge in ovariectomised (OVX) MA rats, and whether exogenous NPY initiates steroid-induced LH surge in OVX old rats. In the first study, NPY release from the ME-arcuate nucleus, as assessed by the push,pull cannula technique, was significantly increased before and during the progesterone-induced LH surge in oestrogen (E2)-primed ovariectomised young rats (2,3 months old). This antecedent increase in NPY release seen in young rats was not apparent in MA rats (11,13 months old) in association with a delayed and attenuated LH surge. In the second study, whereas progesterone failed to induce LH surges in E2 -primed ovariectomised old rats (23,25 months old), intracerebroventricular NPY (0.1,0.5 µg) injections at 1100, 1200 and 13.00 h resulted in LH surge induction in E2 + progesterone-primed ovariectomised old rats. Because increased hypothalamic NPY synthesis and release is obligatory for the preovulatory LH discharge in young rats, the present findings suggest that alteration in NPY release from the ME-arcuate nucleus contributes to the delayed and reduced LH surges in MA rats and may be involved in the subsequent loss of the LH surges in old rats. [source]

Heat shock protein 27 is involved in neurite extension and branching of dorsal root ganglion neurons in vitro

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2006
Kristy L. Williams
Abstract Alteration of the cytoskeleton in response to growth factors and extracellular matrix proteins is necessary for neurite growth. The cytoskeletal components, such as actin and tubulin, can be modified through interaction with other cellular proteins, including the small heat shock protein Hsp27. Our previous work suggested that Hsp27 influences neurite growth, potentially via its phosphorylation state interactions with actin. To investigate further the role of Hsp27 in neurite outgrowth of adult dorsal root ganglion (DRG) neurons, we have both down-regulated endogenous Hsp27 and expressed exogenous Hsp27. Down-regulation of Hsp27 with Hsp27 siRNA resulted in a decrease of neuritic tree length and complexity. In contrast, expression of exogenous Hsp27 in these neurons resulted in an increase in neuritic tree length and branching. Collectively, these results demonstrate that Hsp27 may play a role in neuritic growth via modulation of the actin cytoskeleton. © 2006 Wiley-Liss, Inc. [source]

Alteration of argyrophilic nucleolar organizer region associated (Ag-NOR) proteins in apoptosis-induced human salivary gland cells and human oral squamous carcinoma cells

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2001
Yasuhiro Morimoto
Abstract: The level of argyrophilic nucleolar organizer regions (AgNORs) and AgNOR-associated proteins (Ag-NOR proteins) varies with cell activity, including ribosomal biogenesis occurring in proliferating cells. Proteins associated with some AgNORs are detected by a specific silver staining. To investigate a possible relationship between apoptosis and the AgNORs or Ag-NOR proteins, we examined the changes of AgNORs and Ag-NOR proteins during apoptosis in a human salivary gland cell line, HSG cells, and a human oral squamous carcinoma cell line, SCC-25 cells. Apoptosis was induced by treatment of HSG and SCC-25 cells with okadaic acid. Proteins prepared from HSG and SCC-25 cells treated with varying concentrations of okadaic acid (OA) were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by transferring to transfer membranes and staining for Ag-NOR proteins by modified Western blot analysis. Four major bands (110 kDa, 43 kDa, 39kDa, and 37 kDa) were detected in the proteins obtained from the control cells. The level of the 110-kDa protein decreased in the proteins prepared from OA-induced apoptotic cells; however, the reaction intensity of the other three bands was changed in apoptotic cells. An additional band of an 80-kDa Ag-NOR protein appeared and increased in the apoptotic cells. Cellular fractionation of HSG cells and SCC-25 cells was done with or without apoptotic induction. An 80-kDa Ag-NOR protein was detected in the nuclear fraction prepared from the apoptotic cells, while the 110-kDa protein decreased in the nuclear fraction of these cells. The 110-kDa Ag-NOR protein may be nucleolin (C23) as deduced from its AgNOR staining features, including molecular weight. The 80-kDa protein may be the cleavage product of the 110-kDa protein. In the cell-free apoptotic system, in which intact nuclei of HSG cells were incubated with the cytosol fraction of apoptotic HSG and SCC-25 cells, the 80-kDa Ag-NOR protein was detected in nuclei incubated with the cytosol fraction of apoptotic cells, while the level of the 110-kDa protein decreased. The changes of Ag-NOR proteins in nuclei prepared from SCC-25 cells incubated with cytosol fractions prepared from HSG and SCC-25 cells were identical to those of the HSG cells. The alternation of AgNORs in apoptosis-induced HSG cells was also examined using double staining with Hoechst 33342 and silver nitrate. Hoechst staining revealed typical apoptotic nuclei, which exhibited highly fluorescent condensed chromatin in OA-treated HSG cells. Silver grains representing AgNORs were not detected in the cells undergoing apoptosis. The dual-imposition view confirmed that AgNORs, which are visible as dots in nucleoli in the control cells, disappeared from the apoptotic nuclei of HSG cells. Our results indicate that the 110-kDa nucleolar Ag-NOR protein is associated with apoptosis and is cleaved during apoptosis. [source]

Herpesviruses in human periodontal disease

JOURNAL OF PERIODONTAL RESEARCH, Issue 1 2000
Adolfo Contreras
Recent studies have identified various herpesviruses in human periodontal disease. Epstein,Barr virus type 1 (EBV-1) infects periodontal B-lymphocytes and human cytomegalovirus (HCMV) infects periodontal monocytes/macrophages and T-lymphocytes. EBV-1, HCMV and other herpesviruses are present more frequently in periodontitis lesions and acute necrotizing ulcerative gingivitis-lesions than in gingivitis or periodontally healthy sites. Reactivation of HCMV in periodontitis lesions tends to be associated with progressing periodontal disease. Herpesvirus-associated periodontitis lesions harbor elevated levels of periodontopathic bacteria, including Acrinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteriodes forsythus, Prevotella intermedia, Prevotella nigrescens and Treponema denticola. It may be that active periodontal herpesvirus infection impairs periodontal defenses, thereby permitting subgingival overgrowth of periodontopathic bacteria. Alteration between latent and active herpesvirus infection in the periodontium might lead to transient local immunosuppression and explain in part the episodic progressive nature of human periodontitis. Tissue tropism of herpesvirus infections might help explain the localized pattern of tissue destruction in periodontitis. Absence of herpesvirus infection or viral reactivation might explain why some individuals carry periodontopathic bacteria while still maintaining periodontal health. Further studies are warranted to delineate whether the proposed herpesvirus-periodontopathic bacteria model might account for some of the pathogenic features of human periodontal disease. [source]

Alteration of the intravenous pharmacokinetics of a synthetic ozonide antimalarial in the presence of a modified cyclodextrin

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2006
Susan A. Charman
Abstract The pharmacokinetic profile and renal clearance of a novel synthetic ozonide antimalarial (1) was found to be significantly altered when intravenously administered to rats as a cyclodextrin-based formulation (0.1 M Captisol®, a sulfobutylether ,-cyclodextrin derivative (SBE7 -,-CD)) compared to a cyclodextrin-free isotonic buffered glucose formulation. There was an 8.5-fold decrease in the steady-state blood volume of distribution, a 6.6-fold decrease in the mean residence time and a greater than 200-fold increase in renal clearance of 1 when administered in the cyclodextrin formulation. Analysis of the whole blood and plasma concentration profiles revealed an essentially constant blood to plasma ratio when 1 was administered in the cyclodextrin-free formulation, whereas this ratio changed as a function of time when administered in the presence of the cyclodextrin derivative. It is postulated that the observed differences were due to a very strong complexation interaction between 1 and the cyclodextrin, resulting in a slow dissociation of the complex in vivo, and altered distribution and excretion profiles. Preliminary studies using isothermal titration calorimetry (ITC) indicated that the association constant for the 1/Captisol® complex was approximately two orders of magnitude higher than reported for typical drug/cyclodextrin complexes. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:256,267, 2006 [source]