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1.  Antibiotic Susceptibilities of Pseudomonas aeruginosa Isolated from Blood Samples and Antibiotic Utilization in a University Hospital in Japan 
Infectious Diseases and Therapy  2015;4(2):213-218.
Introduction
Pseudomonas aeruginosa is one of the most important causes of nosocomial infection. Several reports indicated a correlation of antimicrobial usages and declined susceptibilities. In this report, we evaluated their relation in a tertiary care teaching hospital in Tokyo, Japan for 4 years.
Methods
We evaluated the susceptibilities of 149 strains of P. aeruginosa isolated from blood samples and consumption of anti-pseudomonal antibiotics as antimicrobial use density from 2009 to 2012 in the University of Tokyo Hospital in Tokyo, Japan.
Results
Usages of carbapenems and anti-pseudomonal cephalosporins decreased 44% and 31% from 2009 to 2011, and then increased 30% and 24% in 2012, respectively. Usage of piperacillin–tazobactam increased 87% from 2009 to 2012, which was introduced in the hospital in 2008. Consumption of fluoroquinolones and aminoglycoside remained low in those years. Susceptibilities to cephalosporins, carbapenems (except for panipenem–betamipron), penicillins, and fluoroquinolones declined between 22% and 39% in 2010, increased in the range of 16–31% in 2011, and increased by 1–14% in 2012. Susceptibility of panipenem–betamipron ranged between 25% and 32%. Susceptibility to aminoglycoside was more than 90% during this period. No relationship between antimicrobial usages and susceptibilities of P. aeruginosa was observed.
Conclusion
Susceptibilities of P. aeruginosa did not correlate with the usage of antibiotics in our hospital. Several infection control measures and other factors might contribute to changing the susceptibilities of bacteria.
Electronic supplementary material
The online version of this article (doi:10.1007/s40121-015-0066-x) contains supplementary material, which is available to authorized users.
doi:10.1007/s40121-015-0066-x
PMCID: PMC4471057  PMID: 25991512
Antimicrobial usage; Pseudomonas aeruginosa; Susceptibility
2.  Antibiotic Susceptibilities of Pseudomonas aeruginosa Isolated from Blood Samples and Antibiotic Utilization in a University Hospital in Japan 
Infectious Diseases and Therapy  2015;4(2):213-218.
Introduction
Pseudomonas aeruginosa is one of the most important causes of nosocomial infection. Several reports indicated a correlation of antimicrobial usages and declined susceptibilities. In this report, we evaluated their relation in a tertiary care teaching hospital in Tokyo, Japan for 4 years.
Methods
We evaluated the susceptibilities of 149 strains of P. aeruginosa isolated from blood samples and consumption of anti-pseudomonal antibiotics as antimicrobial use density from 2009 to 2012 in the University of Tokyo Hospital in Tokyo, Japan.
Results
Usages of carbapenems and anti-pseudomonal cephalosporins decreased 44% and 31% from 2009 to 2011, and then increased 30% and 24% in 2012, respectively. Usage of piperacillin–tazobactam increased 87% from 2009 to 2012, which was introduced in the hospital in 2008. Consumption of fluoroquinolones and aminoglycoside remained low in those years. Susceptibilities to cephalosporins, carbapenems (except for panipenem–betamipron), penicillins, and fluoroquinolones declined between 22% and 39% in 2010, increased in the range of 16–31% in 2011, and increased by 1–14% in 2012. Susceptibility of panipenem–betamipron ranged between 25% and 32%. Susceptibility to aminoglycoside was more than 90% during this period. No relationship between antimicrobial usages and susceptibilities of P. aeruginosa was observed.
Conclusion
Susceptibilities of P. aeruginosa did not correlate with the usage of antibiotics in our hospital. Several infection control measures and other factors might contribute to changing the susceptibilities of bacteria.
Electronic supplementary material
The online version of this article (doi:10.1007/s40121-015-0066-x) contains supplementary material, which is available to authorized users.
doi:10.1007/s40121-015-0066-x
PMCID: PMC4471057  PMID: 25991512
Antimicrobial usage; Pseudomonas aeruginosa; Susceptibility
3.  Encouragement of Enzyme Reaction Utilizing Heat Generation from Ferromagnetic Particles Subjected to an AC Magnetic Field 
PLoS ONE  2015;10(5):e0127673.
We propose a method of activating an enzyme utilizing heat generation from ferromagnetic particles under an ac magnetic field. We immobilize α-amylase on the surface of ferromagnetic particles and analyze its activity. We find that when α-amylase/ferromagnetic particle hybrids, that is, ferromagnetic particles, on which α-amylase molecules are immobilized, are subjected to an ac magnetic field, the particles generate heat and as a result, α-amylase on the particles is heated up and activated. We next prepare a solution, in which α-amylase/ferromagnetic particle hybrids and free, nonimmobilized chitinase are dispersed, and analyze their activities. We find that when the solution is subjected to an ac magnetic field, the activity of α-amylase immobilized on the particles increases, whereas that of free chitinase hardly changes; in other words, only α-amylase immobilized on the particles is selectively activated due to heat generation from the particles.
doi:10.1371/journal.pone.0127673
PMCID: PMC4437648  PMID: 25993268
4.  Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention 
PPAR Research  2015;2015:646423.
Thiazolidinediones (TZDs) are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ) and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC) in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema.
doi:10.1155/2015/646423
PMCID: PMC4446477  PMID: 26074951
5.  Species differences in regulation of renal proximal tubule transport by certain molecules 
World Journal of Nephrology  2015;4(2):307-312.
Renal proximal tubules (PTs) play important roles in the regulation of acid/base, plasma volume and blood pressure. Recent studies suggest that there are substantial species differences in the regulation of PT transport. For example, thiazolidinediones (TZDs) are widely used for the treatment of type 2 diabetes mellitus, but the use of TZDs is associated with fluid overload. In addition to the transcriptional enhancement of sodium transport in distal nephrons, TZDs rapidly stimulate PT sodium transport via a non-genomic mechanism depending on peroxisome proliferator activated receptor γ/Src/epidermal growth factor receptor (EGFR)/MEK/ERK. In mouse PTs, however, TZDs fail to stimulate PT transport probably due to constitutive activation of Src/EGFR/ERK pathway. This unique activation of Src/ERK may also affect the effect of high concentrations of insulin on mouse PT transport. On the other hand, the effect of angiotensin II (Ang II) on PT transport is known to be biphasic in rabbits, rats, and mice. However, Ang II induces a concentration-dependent, monophasic transport stimulation in human PTs. The contrasting responses to nitric oxide/guanosine 3’,5’-cyclic monophosphate pathway may largely explain these different effects of Ang II on PT transport. In this review, we focus on the recent findings on the species differences in the regulation of PT transport, which may help understand the species-specific mechanisms underlying edema formation and/or hypertension occurrence.
doi:10.5527/wjn.v4.i2.307
PMCID: PMC4419141  PMID: 25949945
Renal proximal tubule; Thiazolidinediones; Peroxisome proliferator activated receptor γ; Insulin; Angiotensin II; Nitric oxide
6.  A Stable Chimeric Fibroblast Growth Factor (FGF) Can Successfully Replace Basic FGF in Human Pluripotent Stem Cell Culture 
PLoS ONE  2015;10(4):e0118931.
Fibroblast growth factors (FGFs) are essential for maintaining self-renewal in human embryonic stem cells and induced pluripotent stem cells. Recombinant basic FGF (bFGF or FGF2) is conventionally used to culture pluripotent stem cells; however, because of the instability of bFGF, repeated addition of fresh bFGF into the culture medium is required in order to maintain its concentration. In this study, we demonstrate that a heat-stable chimeric variant of FGF, termed FGFC, can be successfully used for maintaining human pluripotent stem cells. FGFC is a chimeric protein composed of human FGF1 and FGF2 domains that exhibits higher thermal stability and protease resistance than do both FGF1 and FGF2. Both human embryonic stem cells and induced pluripotent stem cells were maintained in ordinary culture medium containing FGFC instead of FGF2. Comparison of cells grown in FGFC with those grown in conventional FGF2 media showed no significant differences in terms of the expression of pluripotency markers, global gene expression, karyotype, or differentiation potential in the three germ lineages. We therefore propose that FGFC may be an effective alternative to FGF2, for maintenance of human pluripotent stem cells.
doi:10.1371/journal.pone.0118931
PMCID: PMC4388338  PMID: 25850016
7.  Regulatory roles of nitric oxide and angiotensin II on renal tubular transport 
World Journal of Nephrology  2014;3(4):295-301.
Renal tubules regulate blood pressure and humoral homeostasis. Mediators that play a significant role in regulating the transport of solutes and water include angiotensin II (AngII) and nitric oxide (NO). AngIIcan significantly raise blood pressure via effects on the heart, vasculature, and renal tubules. AngII generally stimulates sodium reabsorption by triggering sodium and fluid retention in almost all segments of renal tubules. Stimulation of renal proximal tubule (PT) transport is thought to be essential for AngII-mediated hypertension. However, AngII has a biphasic effect on in vitro PT transport in mice, rats, and rabbits: stimulation at low concentrations and inhibition at high concentrations. On the other hand, NO is generally thought to inhibit renal tubular transport. In PTs, NO seems to be involved in the inhibitory effect of AngII. A recent study reports a surprising finding: AngII has a monophasic stimulatory effect on human PT transport. Detailed analysis of signalling mechanisms indicates that in contrast to other species, the human NO/guanosine 3’,5’-cyclic monophosphate/extracellular signal-regulated kinase pathway seems to mediate this effect of Ang II on PT transport. In this review we will discuss recent progress in understanding the effects of AngII and NO on renal tubular transport.
doi:10.5527/wjn.v3.i4.295
PMCID: PMC4220364  PMID: 25374825
Angiotensin II; Nitric oxide; Proximal tubules; Thick ascending limb; Distal tubules; Na+ transport
8.  Roles of Renal Proximal Tubule Transport in Acid/Base Balance and Blood Pressure Regulation 
BioMed Research International  2014;2014:504808.
Sodium-coupled bicarbonate absorption from renal proximal tubules (PTs) plays a pivotal role in the maintenance of systemic acid/base balance. Indeed, mutations in the Na+-HCO3− cotransporter NBCe1, which mediates a majority of bicarbonate exit from PTs, cause severe proximal renal tubular acidosis associated with ocular and other extrarenal abnormalities. Sodium transport in PTs also plays an important role in the regulation of blood pressure. For example, PT transport stimulation by insulin may be involved in the pathogenesis of hypertension associated with insulin resistance. Type 1 angiotensin (Ang) II receptors in PT are critical for blood pressure homeostasis. Paradoxically, the effects of Ang II on PT transport are known to be biphasic. Unlike in other species, however, Ang II is recently shown to dose-dependently stimulate human PT transport via nitric oxide/cGMP/ERK pathway, which may represent a novel therapeutic target in human hypertension. In this paper, we will review the physiological and pathophysiological roles of PT transport.
doi:10.1155/2014/504808
PMCID: PMC4058521  PMID: 24982885
9.  Curcumin and 5-Fluorouracil-loaded, folate- and transferrin-decorated polymeric magnetic nanoformulation: a synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia 
The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU]) and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes) by initiating early and late apoptosis.
doi:10.2147/IJN.S49882
PMCID: PMC3891567  PMID: 24531392
nanotechnology; curcumin; 5FU; folate; transferrin; PLGA nanoparticle; magnetic hyperthermia
10.  Cholesterol Accumulation Regulates the Expression of Macrophage Proteins Implicated In Proteolysis and Complement Activation 
Objective
Cholesterol accumulation by macrophages plays a key role in atherogenesis. To begin to develop a global picture of this process, we used proteomics and transcriptomics to analyze foam cells generated with acetyl-LDL, a classic ligand for scavenger receptors.
Methods and Results
Tandem mass spectrometry and stringent statistical analysis revealed that foam cells differentially expressed 15 of the 542 proteins (2.8%) detected in macrophage-conditioned medium. Apolipoprotein E was one of the most up-regulated proteins, confirming that proteins involved in lipid metabolism are important targets for regulation by sterol accumulation. However, levels of proteins linked to complement activation and lysosomal proteolysis also changed markedly. Transcriptional analysis demonstrated that 698 of 19,700 genes (3.5%) were regulated in foam cells, including many genes important in sterol metabolism. We also found that cholesterol accumulation regulated genes implicated in complement activation, but failed to affect genes linked to proteolysis and macrophage polarization. Changes in protein levels in macrophage-conditioned medium were largely independent of changes in mRNA levels.
Conclusions
Loading sterol into macrophages regulates levels of complement proteins and lysosomal proteases—key players in the immune system and plaque rupture. Posttranscriptional mechanisms appear important for controlling levels of most of the proteins detected in macrophage medium.
doi:10.1161/ATVBAHA.112.300383
PMCID: PMC3501207  PMID: 23042816
cholesterol; proteolysis; complement; macrophage; atherosclerosis
11.  Molecular mechanisms of renal and extrarenal manifestations caused by inactivation of the electrogenic Na+-HCO3− cotransporter NBCe1 
The electrogenic Na+-HCO3− cotransporter NBCe1 plays an essential role in bicarbonate absorption from renal proximal tubules, but also mediates the other biological processes in extrarenal tissues such as bicarbonate secretion from pancreatic ducts, maintenance of tissue homeostasis in eye, enamel maturation in teeth, or local pH regulation in synapses. Homozygous mutation in NBCe1 cause proximal renal tubular acidosis (pRTA) associated with extrarenal manifestations such as short stature, ocular abnormalities, enamel abnormalities, and migraine. Functional analyses of NBCe1 mutants using different expression systems suggest that at least a 50% reduction of the transport activity may be required to induce severe pRTA. In addition to functional impairments, some NBCe1 mutants show trafficking defects. Some of the pRTA-related NBCe1 mutants showing the cytoplasmic retention have been shown to exert a dominant negative effect through hetero-oligomer complexes with wild-type NBCe1 that may explain the occurrence of extrarenal manifestations in the heterozygous carries of NBCe1 mutations. Both NBCe1 knockout (KO) and W516X knockin (KI) mice showed very severe pRTA and reproduced most of the clinical manifestations observed in human pRTA patients. Functional analysis on isolated renal proximal tubules from W516X KI mice directly confirmed the indispensable role of NBCe1 in bicarbonate absorption from this nephron segment. In this review, we will focus on the molecular mechanisms underling the renal and extrarenal manifestations caused by NBCe1 inactivation.
doi:10.3389/fphys.2013.00270
PMCID: PMC3787273  PMID: 24101904
NBCe1; pRTA; short stature; ocular abnormalities; migraine; enamel abnormalities; dominant negative effect
12.  Role of renal proximal tubule transport in thiazolidinedione-induced volume expansion 
World Journal of Nephrology  2012;1(5):146-150.
Thiazolidinediones (TZDs), pharmacological activators of peroxisome-proliferator-activated receptors γ (PPARγ), significantly improve insulin resistance and lower plasma glucose concentrations. However, the use of TZDs is associated with plasma volume expansion, the mechanism of which has been a matter of controversy. Originally, PPARγ-mediated enhanced transcription of the epithelial Na channel (ENaC) γ subunit was thought to play a central role in TZD-induced volume expansion. However, later studies suggested that the activation of ENaC alone could not explain TZD-induced volume expansion. We have recently shown that TZDs rapidly stimulate sodium-coupled bicarbonate absorption from renal proximal tubule (PT) in vitro and in vivo. TZD-induced transport stimulation was dependent on PPARγ/Src/EGFR/ERK, and observed in rat, rabbit and human. However, this stimulation was not observed in mouse PTs where Src/EGFR is constitutively activated. Analysis in mouse embryonic fibroblast cells confirmed the existence of PPARγ/Src-dependent non-genomic signaling, which requires the ligand binding ability but not the transcriptional activity of PPARγ. The TZD-induced enhancement of association between PPARγ and Src supports an obligatory role for Src in this signaling. These results support the view that TZD-induced volume expansion is multifactorial. In addition to the PPARγ-dependent enhanced expression of the sodium transport system(s) in distal nephrons, the PPARγ-dependent non-genomic stimulation of renal proximal transport may be also involved in TZD-induced volume expansion.
doi:10.5527/wjn.v1.i5.146
PMCID: PMC3782215  PMID: 24175252
Thiazolidinediones; Peroxisome-proliferator-activated receptors γ; Volume expansion; Edema; NBCe1; NHE3; Epithelial Na channel
13.  Bilateral Endoscopic Medial Maxillectomy for Bilateral Inverted Papilloma 
Case Reports in Otolaryngology  2012;2012:215847.
Inverted papilloma (IP) is a benign tumor of the nasal cavity and paranasal sinuses that is unilateral in most cases. Bilateral IP, involving both sides of the nasal cavity and sinuses, is extremely rare. This paper describes a large IP that filled in both sides of the nasal cavity and sinuses, mimicking association with malignancy. The tumor was successfully treated by bilateral endoscopic medial maxillectomy (EMM). The patient is without evidence of the disease 24 months after surgery. If preoperative diagnosis does not confirm the association with malignancy in IP, endoscopic sinus surgery (ESS) should be selected, and ESS, including EMM, is a good first choice of the treatment for IP.
doi:10.1155/2012/215847
PMCID: PMC3420519  PMID: 22953103
14.  Endoscopic Endonasal Transturbinate Approach to the Pterygopalatine Fossa in the Management of Juvenile Nasopharyngeal Angiofibromas 
Case Reports in Otolaryngology  2012;2012:786262.
Pterygopalatine fossa (PPF) is a difficult-to-access anatomic area located behind the posterior wall of the maxillary sinus. Juvenile nasopharyngeal angiofibroma (JNA) often affects this area, and the management of feeding artery to the tumor is important in the surgery. Endoscopic endonasal approach to the PPF without endangering all other nasal structures is useful in the management of JNA. We describe a new approach to the PPF, endoscopic transturbinate approach, which is effective in the management of JNA. Submucous inferior turbinoplasty was performed, and sphenopalatine artery, the feeder to the tumor, was identified at the sphenopalatine foramen. The posterior wall of maxillary sinus was removed. Internal maxillary artery was identified in the PPF and was ligated with a hemoclip. The tumor in the PPF was pushed into the nasal cavity. These procedures were all performed via submucous turbinate tunnel. Then, the tumor was successfully removed in en bloc from the nasal cavity by transnasal approach without ethmoidectomy. This approach improves accessibility and visualization in the PPF and potential to reduce intraoperative bleeding due to ligation of the feeder safely without touching the tumor. Endoscopic transturbinate approach is effective in the management of early stage of JNA.
doi:10.1155/2012/786262
PMCID: PMC3420430  PMID: 22953122
15.  Wegener's Granulomatosis with Extensive Bone Abnormalities Mimicking Fungal Sinusitis 
Case Reports in Otolaryngology  2012;2012:103403.
Abnormalities of the underlying bone of the paranasal sinuses have sometimes been shown in Wegener's granulomatosis (WG). We describe an interesting case of WG with extensive bone abnormalities in the sinuses mimicking fungal sinusitis. A 30-year-old woman presented with intermittent unilateral epistaxis. Biopsy was performed for the granulation tissue in the right nasal cavity, and she was diagnosed as having WG. Computed tomography (CT) revealed a ring-like calcification, mimicking a fungus ball, in the right maxillary sinus. Endoscopic sinus surgery was performed to confirm the diagnosis. A spherical bony structure, surrounded by granulation tissue, was identified in the maxillary sinus. The wall of the “bony ball” was fragile, like an egg shell. No fungus was found in the sinus. Thus, the extensive bone abnormalities were due to WG.
doi:10.1155/2012/103403
PMCID: PMC3420613  PMID: 22953096
16.  Functional Roles of Electrogenic Sodium Bicarbonate Cotransporter NBCe1 in Ocular Tissues 
Electrogenic Na+-HCO3- cotransporter NBCe1 is expressed in several tissues such as kidney, eye, and brain, where it may mediate distinct biological processes. In particular, NBCe1 in renal proximal tubules is essential for the regulation of systemic acid/base balance. On the other hand, NBCe1 in eye may be indispensable for the maintenance of tissue homeostasis. Consistent with this view, homozygous mutations in NBCe1 cause severe proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataract. The widespread expression of NBCe1 in eye suggests that the inactivation of NBCe1 per se may be responsible for the occurrence of these ocular abnormalities. In this review, we discuss about physiological and pathological roles of NBCe1 in eye.
doi:10.2174/1874364101206010036
PMCID: PMC3394102  PMID: 22798968
NBCe1; proximal renal tubular acidosis; band keratopathy; glaucoma; cataract.
17.  HDL suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide 
Circulation  2010;122(19):1919-1927.
Background
High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that HDL might also inhibit atherogenesis by combating inflammation.
Methods and Results
To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 30% (277 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDL’s ability to inhibit gene expression was independent of macrophage cholesterol stores. Immunofluorescent studies suggested that HDL promoted TRAM translocation to intracellular compartments, which impaired subsequent signaling by TLR4 and TRIF. To examine the potential in vivo relevance of the pathway, we used mice deficient in apolipoprotein (apo) A-I, HDL’s major protein. After infection with Salmonella typhimurium, a Gram-negative bacterium that expresses LPS, apoA-I–deficient mice had 6-fold higher plasma levels of interferon-β –a key regulator of the type I interferon response– than did wild-type mice.
Conclusions
HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection.
doi:10.1161/CIRCULATIONAHA.110.961193
PMCID: PMC2988582  PMID: 20974999
Lipid-raft; MyD88; chemokine; cytokine; interferon regulatory factor 7
18.  Insulin Resistance, Obesity, Hypertension, and Renal Sodium Transport 
Sodium transport through various nephron segments is quite important in regulating sodium reabsorption and blood pressure. Among several regulators of this process, insulin acts on almost all the nephron segments and is a strong enhancer of sodium reabsorption. Sodium-proton exchanger type 3 (NHE3) is a main regulator of sodium reabsorption in the luminal side of proximal tubule. In the basolateral side of the proximal tubule, sodium-bicarbonate cotransporter (NBCe1) mediates sodium and bicarbonate exit from tubular cells. In the distal nephron and the connecting tubule, epithelial sodium channel (ENaC) is of great importance to sodium reabsorption. NHE3, NBCe1, and ENaC are all regulated by insulin. Recently with-no-lysine (WNK) kinases, responsible for familial hypertension, stimulating sodium reabsorption in the distal nephron, have been found to be also regulated by insulin. We will discuss the regulation of renal sodium transport by insulin and its roles in the pathogenesis of hypertension in insulin resistance.
doi:10.4061/2011/391762
PMCID: PMC3095959  PMID: 21629870
19.  Expression of bone morphogenic protein in sinonasal inverted papilloma with new bone formation 
Allergy & Rhinology  2011;2(1):16-20.
Inverted papilloma (IP) is a common benign tumor in the nose and sinus. Osteogenesis in sinonasal IP is extremely rare; to date, only five cases of IP with new bone formation appear in the literature. In addition, the mechanism of osteogenesis in IP remains unclear. Here, we describe three cases of IP with new bone formation and an investigation into a possible role for bone morphogenic protein (BMP) in osteogenesis. Of three patients with sinonasal IP with new bone formation, two were treated by endoscopic sinus surgery and one was followed up with watchful waiting. Tumor tissues were subjected to immunohistochemistry to detect BMP expression. The patients were successfully treated surgically and showed no evidence of recurrence postoperatively. Follow-up examination is ongoing. Immunohistochemically, the tumors expressed BMP-4 but not BMP-2 or BMP-7. ESS could be successfully used to achieve complete removal of the sinonasal IPs with new bone formation. BMP-4 might be associated with new bone formation in the tumor.
doi:10.2500/ar.2011.2.0004
PMCID: PMC3390124  PMID: 22852110
Bone formation; bone morphogenic protein; endoscopic sinus surgery; inverted papilloma; sinonasal
20.  Sinonasal Schwannoma with New Bone Formation Expressing Bone Morphogenic Protein 
Schwannoma is a benign tumor that arises from the sheath of myelinated nerve fibers and may occur in any part of the body. Osteogenesis in schwannoma is extremely rare and, to date, new bone formation in sinonasal schwannoma has not yet been reported. Here, we describe the first reported case of sinonasal schwannoma with new bone formation. The tumor was successfully treated by endoscopic sinus surgery, and the patient showed no evidence of recurrence 24 months postoperatively. Immunohistochemically, the tumor expressed bone morphogenic protein 4, indicating a possible role of this protein in the new bone formation in schwannomas.
doi:10.1155/2010/154948
PMCID: PMC3010644  PMID: 21197441
21.  Function of the aux and rol genes of the Ri plasmid in plant cell division in vitro 
Plant Signaling & Behavior  2009;4(12):1145-1147.
Auxin-autonomous growth in vitro may be related to the integration and expression of the aux and rol genes from the root-inducing (Ri) plasmid in plant cells infected by agropine-type Agrobacterium rhizogenes. To elucidate the functions of the aux and rol genes in plant cell division, plant cell lines transformed with the aux1 and aux2 genes or with the rolABCD genes were established using tobacco (Nicotiana tabacum) Bright Yellow-2 (BY-2) cells. The introduction of the aux1 and aux2 genes enabled the auxin-autonomous growth of BY-2 cells, but the introduction of the rolABCD genes did not affect the auxin requirement of the BY-2 cells. The results clearly show that the aux genes are necessary for auxinautotrophic cell division, and that the rolABCD genes are irrelevant in auxin autotrophy.
PMCID: PMC2819440  PMID: 20514230
Agrobacterium rhizogenes; auxin-autotrophic cell; auxin biosynthesis; hairy root; plant cell division; Ri plasmid; T-DNA; aux; rol; tobacco BY-2 cells
22.  Analysis of Nucleotide Sequences of Human Parvovirus B19 Genome Reveals Two Different Modes of Evolution, a Gradual Alteration and a Sudden Replacement: a Retrospective Study in Sapporo, Japan, from 1980 to 2008▿  
Journal of Virology  2009;83(21):10975-10980.
There have been no long-term systematic analyses of the molecular epidemiology of human parvovirus B19 (B19V). We investigated the variations of nucleotide sequences of B19V strains collected in Sapporo, Japan, from 1980 to 2008. In that period, six outbreaks of erythema infectiosum occurred regularly at 5-year intervals. The B19V strains collected successively, regardless of the outbreak, were analyzed for nucleotide variation in the subgenomic NS1-VP1u junction. The isolated strains can be classified into 10 subgroups. Two patterns of change of endemic strains were observed. One was a dynamic replacement of strains that occurred almost every 10 years, and the other was a gradual change consisting of an accumulation of point mutations.
doi:10.1128/JVI.00273-09
PMCID: PMC2772762  PMID: 19710152
23.  Expression of tumor necrosis factor-alpha converting enzyme and matrix metalloproteinase-3 in proliferated synovium in a patient with synovitis-acne-pustulosis-hyperostosis-osteitis syndrome: a case report 
Introduction
Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is a rare disorder. The etiology remains unknown and the treatment is still empirical. Synovitis is one of the major manifestations, but information on histopathological features is still lacking. In this case, we investigated the histopathological features of SAPHO syndrome synovitis.
Case presentation
We present the case of a 53-year-old Japanese woman with SAPHO syndrome accompanied by marked knee synovitis and palmoplantar pustulosis. We found abundant sterile joint fluid in the right knee, and a blood test showed abnormally high values of C-reactive protein (17.26 mg/dl) and matrix metalloproteinase-3 (800 ng/ml). Arthroscopic surgery revealed marked proliferation of villous synovial tissues similar to rheumatoid arthritis and standard microscopic findings were also similar to rheumatoid arthritis. Furthermore, for the first time, we demonstrated by immunohistochemistry the expression of tumor necrosis factor-alpha (TNF-α) converting enzyme, TNF-α and matrix metalloproteinase-3 in the proliferated synovial lining cells. After arthroscopic synovectomy, her knee symptoms immediately diminished and laboratory data (matrix metalloproteinase-3 and C-reactive protein) normalized within 2 weeks of surgery.
Conclusion
We demonstrate the expression of TNF-α converting enzyme, TNF-α and matrix metalloproteinase-3 in SAPHO syndrome synovitis for the first time and also show, both macro- and microscopically, the similarity between SAPHO syndrome and rheumatoid arthritis synovitis. These new findings support the recently reported successful treatment of SAPHO syndrome with antirheumatic drugs, especially with anti-TNF-α agents.
doi:10.4076/1752-1947-3-9123
PMCID: PMC2827166
24.  The DNA-recognition mode shared by archaeal feast/famine-regulatory proteins revealed by the DNA-binding specificities of TvFL3, FL10, FL11 and Ss-LrpB 
Nucleic Acids Research  2009;37(13):4407-4419.
The DNA-binding mode of archaeal feast/famine-regulatory proteins (FFRPs), i.e. paralogs of the Esherichia coli leucine-responsive regulatory protein (Lrp), was studied. Using the method of systematic evolution of ligands by exponential enrichment (SELEX), optimal DNA duplexes for interacting with TvFL3, FL10, FL11 and Ss-LrpB were identified as TACGA[AAT/ATT]TCGTA, GTTCGA[AAT/ATT]TCGAAC, CCGAAA[AAT/ATT]TTTCGG and TTGCAA[AAT/ATT]TTGCAA, respectively, all fitting into the form abcdeWWWedcba. Here W is A or T, and e.g. a and a are bases complementary to each other. Apparent equilibrium binding constants of the FFRPs and various DNA duplexes were determined, thereby confirming the DNA-binding specificities of the FFRPs. It is likely that these FFRPs recognize DNA in essentially the same way, since their DNA-binding specificities were all explained by the same pattern of relationship between amino-acid positions and base positions to form chemical interactions. As predicted from this relationship, when Gly36 of TvFL3 was replaced by Thr, the b base in the optimal DNA duplex changed from A to T, and, when Thr36 of FL10 was replaced by Ser, the b base changed from T to G/A. DNA-binding characteristics of other archaeal FFRPs, Ptr1, Ptr2, Ss-Lrp and LysM, are also consistent with the relationship.
doi:10.1093/nar/gkp378
PMCID: PMC2715240  PMID: 19468044
25.  Albinism and cell viability in cycloartenol synthase deficient Arabidopsis 
Plant Signaling & Behavior  2008;3(11):978-980.
Phenotypes of Arabidopsis thaliana that carry mutations in CYCLOARTENOL SYNTHASE 1 (CAS1) which is required in sterol biosynthesis have been described. Knockout mutant alleles are responsible of a male-specific transmission defect. Plants carrying a weak mutant allele cas1-1 accumulate 2,3-oxidosqualene, the substrate of CAS1, in all analyzed organs. Mutant cas1-1 plants develop albino inflorescence shoots that contain low amount of carotenoids and chlorophylls. The extent of this albinism, which affects Arabidopsis stems late in development, may be modulated by the light/dark regime. The fact that chloroplast differentiation and pigment accumulation in inflorescence shoots are associated with a low CAS1 expression could suggest the involvement of 2,3-oxidosqualene in a yet unknown regulatory mechanism linking the sterol biosynthetic segment, located in the cytoplasm, and the chlorophyll and carotenoid biosynthetic segments, located in the plastids, in the highly complex terpenoid network. CAS1 loss of function in a mosaic analysis of seedlings further demonstrated that leaf albinism associated with an accumulation of 2,3-oxidosqualene is a novel phenotype for plant sterol deficient mutant.
PMCID: PMC2633748  PMID: 19704425
albinism; cell viability; sterol; terpenoid; light

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