Endogenous Fusarium Endophthalmitis During Treatment for Acute Myeloid Leukemia,Successfully Treated with 25-Gauge Vitrectomy and Antifungal Medications

Endogenous fungal endophthalmitis (EFE) caused by disseminated fusariosis is a rare condition that generally has a poor outcome, even with intensive therapy. Here, we describe a case in which this type of EFE was diagnosed with vitreous sampling and was successfully treated with 25-gauge vitrectomy and antifungals, including liposomal amphotericin B and voriconazole. A 16-year-old male patient undergoing treatment for acute myeloid leukemia complained of eye pain and blurred vision in his right eye. Treatment was initiated for a vitreous opacity, possibly associated with herpetic retinitis, but the patient worsened and he was referred to us. Right-eye visual acuity was limited to light perception. We suspected endogenous endophthalmitis and performed 25-gauge vitrectomy with antibiotic perfusion of ceftazidime, vancomycin, and voriconazole. Vitreous culturing revealed the presence of Fusarium solani species complex, and enhanced computed tomography revealed disseminated fusariosis lesions in the lung, spleen, and the soft tissue of the left upper arm. The patient received antifungal treatment with liposomal amphotericin B and voriconazole, and these conditions were eliminated. Visual acuity recovered to 20/400 after additional vitrectomy for tractional retinal detachment and was maintained at this level during the 6-month follow-up period. The success of our treatment allowed the capture of optical coherence tomography images of the retina during fusarium-associated endogenous endophthalmitis and the follow-up period. Furthermore, this case showed that immediate vitrectomy for suspected EFE and intensive treatment can lead to a good clinical outcome.     

Hydrogels of N-acylchitosans and their cellulose composites generated from the aqueous alkaline solutions

Hydrogels of N-acetyl and N-propionylchitosans were prepared form aqueous solutions of sodium N-acylchitosan salts (alkaline N-acylchitosans) and sodium N-acylchitosan xanthate [O-(sodium thio)thiocarbonyl N-acylchitosan], respectively, by standing at room temperature and on heating. Novel hydrogels of N-acetylchitosan-cellulose and N-propionylchitosan-cellulose composites were also prepared from sodium cellulose xanthate [O-(sodiumthio)thiocarbonyl cellulose] solutions mixed with sodium N-acylchitosan salts and with sodium N-acylchitosan xanthates, respectively.     

Organization of gene structure and expression of nuclear factor 1 family in rat.

The nuclear factor 1 (NF1) family proteins are encoded by four different genes (Nfia, Nfib, Nfic and Nfix) and regulate gene expression and DNA replication. All four genes bear many splicing isoforms, but the biological function of each of them awaits further characterization. We have previously isolated several splicing variant cDNAs derived from four NF1 genes of rat, and elucidated the structure of the rat Nfia gene. In this study, we determined the genomic organization and nucleotide sequences of the exon/intron boundaries of the rat Nfib, Nfic and Nfix genes in silico. We also constructed plasmids including entire open reading frames (ORFs) of NF1 isoforms and verified the expression of them in vitro. This information is made available for the production of NF1 knockout animals and expression of NF1 isoforms in vivo to elucidate the physiological function of NF1 proteins and to reveal the functional differences between NF1 splicing variants.     

Analysis of K Inactivation and TEA Action in the Supramedullary Cells of Puffer

Under the voltage clamp condition, the K inactivation was analyzed in cells bathed in the isosmotic KCl Lophius-Ringer solution. After conditioning hyperpolarization, the cells respond to depolarizations with increased K permeability, which in turn is decreased during maintained depolarizations. The steady-state levels of the K inactivation as a function of the membrane potential are related by an S-shaped curve similar to that which describes the steady-state Na inactivation in the squid giant axon. TEA reduced the K conductance by a factor which is independent of the potential, and without a shift of the inactivation curve along the voltage axis. The rapid phase of the K activation is less susceptible to TEA than the slow phase of the K activation. Hyperpolarizing steps remove the K inactivation, the rate of the removal being faster the larger the hyperpolarization from the standard potential of about -60 mv.     

Crystal structures of cyclomaltohexaose (α-cyclodextrin) complexes with p-chlorophenol and p-cresol

Crystal structures of cyclomaltohexaose (α-cyclodextrin) complexes with p-chlorophenol and p-cresol have been determined by single-crystal X-ray diffraction studies. The space group of the α-cyclodextrin–p-chlorophenol complex is P2₁2₁2₁ with unit cell dimensions of a=15.299(3), b=24.795(5), c=13.447(5) Å, and that of the α-cyclodextrin–p-cresol complex is P2₁ with unit cell dimensions of a=7.927(7), b=13.568(7), c=24.54(1) Å, β=90.41(8)°. In spite of the similar structures of guest molecules, both complexes have different inclusion modes and packing structures.     

Timing of genome duplications relative to the origin of the vertebrates: did cyclostomes diverge before or after?

Two rounds of whole-genome duplications are thought to haveplayed an important role in the establishment of gene repertoiresin vertebrates. These events occurred during chordate evolutionafter the split of the urochordate and cephalochordate lineagesbut before the radiation of extant gnathostomes (jawed vertebrates).During this interval, diverse agnathans (jawless fishes), includingcyclostomes (hagfishes and lampreys), diverged. However, thereis no solid evidence for the timing of these genome duplicationsin relation to the divergence of cyclostomes from the gnathostomelineage. We conducted cDNA sequencing in diverse early vertebratesfor members of homeobox-containing (Dlx and ParaHox) and othergene families that would serve as landmarks for genome duplications.Including these new sequences, we performed a molecular phylogeneticcensus using the maximum likelihood method for 55 gene families.In most of these gene families, we detected many more gene duplicationsbefore the cyclostome–gnathostome split, than after. Manyof these gene families (e.g., visual opsins, RAR, Notch) havemultiple paralogs in conserved, syntenic genomic regions thatmust have been generated by large-scale duplication events.Taken together, this indicates that the genome duplicationsoccurred before the cyclostome–gnathostome split. We proposethat the redundancy in gene repertoires possessed by all vertebrates,including hagfishes and lampreys, was introduced primarily bygenome duplications. Apart from subsequent lineage-specificmodifications, these ancient genome duplication events mightserve generally to distinguish vertebrates from invertebratesat the genomic level.     

Effects of a high-salt diet on adipocyte glucocorticoid receptor and 11-β hydroxysteroid dehydrogenase 1 in salt-sensitive hypertensive rats

High-salt diets decrease insulin sensitivity in salt-sensitive hypertensive rats, and glucocorticoids promote adipocyte growth and may have pathophysiological roles in the metabolic syndrome. The aim of this study was to clarify the relationship between high-salt diet and the adipocyte glucocorticoid hormones in salt-sensitive hypertensive rats. Six-week-old Dahl salt-sensitive (DS) hypertensive rats and salt-resistant (DR) rats were fed a high-salt diet or a normal-salt diet for 4 weeks. Fasting blood glucose (FBG), serum adiponectin, plasma insulin, and corticosterone in plasma and in visceral adipose tissues, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activities in adipose tissues and glucose uptake in isolated muscle were measured. Animals underwent an oral glucose tolerance test (OGTT). The expression of mRNA for glucocorticoid receptor (GR), 11β-HSD1 and tumor necrosis factor-α (TNF-α) in adipose tissues were measured using a real-time PCR. A high-salt diet did not influence FBG; however, decreased 2-deoxy glucose uptake and plasma insulin during OGTT in DS rats. The high-salt diet increased significantly adipose tissue corticosterone concentration and 11β-HSD1 activities, gene expression for GR, 11β-HSD1 and TNF-α in adipose tissues in DS rats compared with DR rats (p < 0.05). The high-salt diet did not influence plasma corticosterone and serum adiponectin concentration in DS and DR rats. These results suggest that changes in GR and 11β-HSD1 in adipose tissue may contribute to insulin sensitivity in salt-sensitive hypertensive rats.     

Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice

Fibrosis is a pathological process characterized by infiltration and proliferation of mesenchymal cells in interstitial space. A substantial portion of these cells is derived from residing non-epithelial and/or epithelial cells that have acquired the ability to migrate and proliferate. The mesenchymal transition is also observed in cancer cells to confer the ability to metastasize. Here, we show that renal fibrosis induced by unilateral ureteral obstruction and metastasis of human cancer xenografts are suppressed by administration of secreted Klotho protein to mice. Klotho is a single-pass transmembrane protein expressed in renal tubular epithelial cells. The extracellular domain of Klotho is secreted by ectodomain shedding. Secreted Klotho protein directly binds to the type-II TGF-β receptor and inhibits TGF-β1 binding to cell surface receptors, thereby inhibiting TGF-β1 signaling. Klotho suppresses TGF-β1-induced epithelial-to-mesenchymal transition (EMT) responses in cultured cells, including decreased epithelial marker expression, increased mesenchymal marker expression, and/or increased cell migration. In addition to TGF-β1 signaling, secreted Klotho has been shown to inhibit Wnt and IGF-1 signaling that can promote EMT. These results have raised the possibility that secreted Klotho may function as an endogenous anti-EMT factor by inhibiting multiple growth factor signaling pathways simultaneously.