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In patients infected with human immunodeficiency virus (HIV)-1 at our hospital, we observed increases in skin and soft-tissue infections (SSTIs) by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Therefore, we analyzed factors related to CA-MRSA infection and performed a molecular epidemiological investigation.HIV-1-infected patients were diagnosed with SSTIs related to S. aureus between 2007 and 2017, and MRSA was classified into community and hospital-acquired types according to published criteria. Information was collected retrospectively from clinical records, and multivariate analysis by logistic regression was performed concerning factors related to CA-MRSA infection. We evaluated the staphylococcal cassette chromosome mec (SCCmec) type, multilocus sequence type, and the presence of genes encoding Panton-Valentine leucocidin (PVL) in 27 MRSA samples isolated during and after 2015.We found 218 episodes of SSTIs in 169 patients, and among initial episodes of SSTIs, the MRSA ratio was higher from 2015 to 2017 relative to that from 2007 to 2014 (88% vs. 44%; p 0.0001). Multivariate analysis showed that in men having sex with men [MSM; odds ratio (OR): 13] and exhibiting onset during and after 2015 (OR: 5.4), CD4These data describe an increased prevalence of SSTIs due to PVL-positive ST8-MRSA-IV, not previously considered epidemic in Japan, in MSM infected with HIV-1 in Osaka, Japan.

Dolutegravir may inhibit creatinine transporters in renal tubules and elevate serum creatinine levels. We investigated the usefulness of glomerular filtration rate (GFR) measured using inulin clearance (Cin), creatinine clearance (Ccr), and estimated GFR based on both serum creatinine (eGFRcre) and serum cystatin C (eGFRcys).HIV-1-infected Japanese patients with suppressed viremia and whose antiretroviral drug was switched to dolutegravir from other drugs were included (n = 108, Study 1). We compared eGFRcre and eGFRcys at the start and after 48 weeks of dolutegravir administration. For the patients providing consent, we measured Cin and Ccr (n = 15, Study 2). We assessed biases and accuracy and compared Cin with eGFRcre, eGFRcys, and Ccr.There were no differences in serum cystatin C and eGFRcys between baseline and at 48 weeks. Moreover, eGFRcre was significantly less accurate (within 30% of measured GFR) than both eGFRcys and Ccr (40% accuracy compared to 93% and 93%, respectively). eGFRcys was significantly less biased than eGFRcre and Ccr (p 0.0001, p = 0.00036, respectively). No significant difference between Cin and eGFRcys was observed. eGFRcys was significantly correlated with Cin (γ = 0.85, p 0.0001).eGFRcys provided the most precise estimate and most closely approximate Cin in HIV-1-infected Japanese patients with suppressed viremia treated with dolutegravir. We demonstrated clinical benefits of inulin clearance and eGFRcys. This is the first study performing inulin clearance for HIV-1-infected individuals and to show data for eGFRcys from a large cohort following a switch to dolutegravir from other antiretroviral agents.

The pathophysiology of bladder leiomyosarcoma, a rare disease with aggressive mesenchymal tumor, is not certain, but its main symptoms are hematuria, dysuria and abdominal pain. Cases described in the literature are few. This report describes a case of a leiomyosarcoma of the urinary bladder in a 49-year-old woman. After CT scanning revealed a heterogeneously enhanced 4-cm mass involving the bladder neck and anterior wall, further examinations detected no metastatic lesion. Cystoscopy and transurethral resection of bladder tumor (TURBT) were performed. The histopathological diagnosis was leiomyosarcoma. Postoperative period was uneventful. The patient experienced complete resolution of urologic symptoms. Repeat-TURBT was performed 70 days after first surgery. The patient has remained disease-free 18 months after surgery. Keywords: Leiomyosarcoma, Nonurothelial bladder tumor, TURBT

Filial imprinting in precocial birds is a useful model for studying early learning and cognitive development, as it is characterized by a well-defined sensitive or critical period. We recently showed that the thyroid hormone 3,5,3′-triiodothyronine (T3) determines the onset of the sensitive period. Moreover, exogenous injection of T3 into the intermediate medial mesopallium (IMM) region (analogous to the associative cortex in mammals) enables imprinting even on post-hatch day 4 or 6 when the sensitive period has been terminated. However, the neural mechanisms downstream from T3 action in the IMM region remain elusive. Here, we analyzed the functional involvement of the intermediate hyperpallium apicale (IMHA) in T3 action. Bilateral excitotoxic ablation of the IMHA prevented imprinting in newly hatched chicks, and also suppressed the recovery of the sensitive period by systemic intra-venous or localized intra-IMM injection of T3 in day-4 chicks. In contrast to the effect in the IMM, direct injection of T3 into the IMHA did not enable imprinting in day-4 chicks. Moreover, bilateral ablation of IMHA after imprinting training impaired recall. These results suggest that the IMHA is critical for memory acquisition downstream following T3 action in the IMM and further, that it receives and retains information stored in the IMM for recall. Furthermore, both an avian adeno-associated viral construct containing an anterograde tracer (wheat-germ agglutinin) and a retrograde tracer (cholera toxin subunit B) revealed neural connections from the IMM to the IMHA. Taken together, our findings suggest that hierarchical processes from the primary area (IMM) to the secondary area (IMHA) are required for imprinting.

Raltegravir (RAL), an HIV integrase inhibitor, is metabolized mainly by UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms in UGT1A1 may cause alterations in the pharmacodynamics of RAL, which is taken twice daily with no dietary restrictions. We compared the effect of two polymorphic alleles in this gene, UGT1A1*6 and UGT1A1*28 on plasma RAL concentrations in Japanese HIV-1-infected patients. Of 114 Japanese HIV-1-infected patients who received RAL, the frequencies of UGT1A1*6 and UGT1A1*28 were 18% and 13%, respectively. The percentage of homozygotes for UGT1A1*6 and UGT1A1*28 was 6% and 4%, respectively, the percentage of compound heterozygotes for UGT1A1*6 and UGT1A1*28 was 2%, and that of heterozygotes for UGT1A1*6 and UGT1A1*28 was 22% and 17%, respectively. RAL plasma trough concentrations were compared for each polymorphism. Significantly higher levels of RAL were observed with patients who were homozygous for UGT1A1*6 (median: 1.0 μg/mL) than for the normal allele (median: 0.11 μg/mL; p = 0.021). Multivariate logistic regression analysis showed that the presence of one or two alleles of UGT1A1*6 or two alleles of UGT1A1*28 were independent factors associated with high RAL plasma trough concentrations (≥ 0.17 μg/mL). These results indicated that UGT1A1*6 and UGT1A1*28 are both factors influencing the RAL plasma trough concentrations in Japanese HIV-1-infected patients.

The diagnosis of non-cirrhotic portal hypertension (NCPH), a rare but potentially life-threatening complication in human immunodeficiency virus (HIV)-positive individuals, often occurs only after the emergence of fatal manifestations such as bleeding of esophageal varices. We herein report a female Japanese HIV patient who developed NCPH approximately 4 years after discontinuation of 65 months of didanosine (ddI) administration. The patient presented with severe ascites, bloody bowel discharge, extreme abdominal swelling, and symptoms of portal hypertension but no sign of liver cirrhosis. Examination revealed esophageal varices, oozing-like bleeding from a wide part of the colon, significant atrophy of the right lobe of the liver, and arterio-portal shunting and recanalization from the left medial segment branch of the portal vein to a paraumbilical vein, but no visible obstruction of the main trunk of the portal vein. Treatment for esophageal varices consisted of coagulation therapy with argon plasma after enforcement by endoscopic sclerotherapy and oral administration of β-blockers for elevated portal blood pressure. The patient has not experienced gastrointestinal bleeding in the approximately 5 years since the diagnosis of NCPH. Reviewing this case suggests the importance of suspecting NCPH in HIV patients with liver dysfunction of unknown etiology with a history of ddI and other purine analogs use, as well as the importance of controlling portal hypertension and esophageal varices in the treatment of NCPH.

Immune reconstitution inflammatory syndrome (IRIS) is an unsolved problem in the treatment of human immunodeficiency virus (HIV)-1 infection. Despite the high seroprevalence of parvovirus B19 (PVB19) among HIV-1-positive patients, reports on PVB19-induced anemia, especially that associated with PVB19-related IRIS, in these patients are limited. We present the case of a man with acquired immunodeficiency syndrome who developed severe transfusion-dependent anemia and was seropositive and borderline positive for immunoglobulin-M and IgG antibodies against PVB19, respectively. PVB19-DNA was also detected in his serum. The patient was diagnosed with pure red cell anemia (PRCA) caused by a primary PVB19 infection and was treated with periodical blood transfusions. However, he subsequently tested negative for IgG antibodies and developed chronic severe anemia with high levels of PVB19 viremia. This indicated a transition from primary to persistent infection. After initiation of highly active antiretroviral therapy, the patient showed an inflammatory reaction with rapid deterioration of anemia and seroconversion of the IgG antibody to PVB19. Subsequently, PRCA was completely resolved, but the patient's serum still contained low levels of PVB19-DNA. Thus, this was a case of IRIS associated with PVB19 infection. Our report highlights the significance of seroconversion to PVB19 in the diagnosis of IRIS and re-emphasizes the finding that persistently high levels of PVB19 viremia after primary infection are probably because of the lack of protective antibodies.

The emergence and transmission of drug-resistant human immunodeficiency virus-1 (HIV-1) compromises antiretroviral treatment for HIV-1. Thus, testing for drug resistance is recommended at diagnosis and before initiating highly active antiretroviral treatment. We conducted an epidemiological study enrolling newly diagnosed patients between 2003 and 2008 in our nationwide surveillance network. In the 6-year study period, the prevalence of drug-resistant HIV-1 among 2573 patients, consisting mainly of Japanese men in their late-30s and infected through male-to-male sexual contacts, followed an increasing trend from 5.9% (16/273) in 2003 to 8.3% (50/605) in 2008. Nucleoside reverse transcriptase inhibitor-associated mutations predominated in each year, with T215 revertants being the most abundant. The predictive factor for drug-resistant HIV-1 transmission was subtype B (OR=2.36; p=0.004), and those for recent HIV-1 infection were male gender (OR=3.79; p=0.009), MSM behavior (OR=1.67; p=0.01), Japanese nationality (OR=2.31; p=0.008), and subtype B (OR=5.64; p

A diepoxide compound derived from trehalose, 2,3-anhyrdo-4,6-O-benzylidene-α- d -allopyranosyl 2,3-anhydro-4,6-O-benzylidene-α- d -allopyranoside, was synthesized and reacted with aliphatic diamines. The ring-opening reaction was carried out in 1-methyl-2-pyrrolidone (NMP) in the presence of triphenylphosphine (TPP), tris(4-methoxyphenyl)phosphine (TMPP) or 2-ehtyl-4-methylimidazole (2E4MIm), as a base catalyst. The reaction of the diepoxide compound with 1,6-diaminohexane yielded a soluble polymer with weight average molecular weight (Mw)∼6300 (GPC) and did not yield insoluble matter. The reaction of the diepoxide compound with N,N′-dimethyl-1,6-diaminohexane yielded a polymer with Mw∼6500 (GPC). The product was soluble in many organic solvents such as NMP, N,N-dimethylformamide (DMF), tetrahydrofuran (THF), acetone, toluene and ethyl acetate. Thermal analysis with differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) revealed that the glass transition temperature of the polymer was ∼100 °C and that the degradation temperature was ∼320 °C.

Our studies concern the mechanisms of synaptic transmission and integration in the basal ganglia network, using immunotoxin-mediated cell targeting. We generated transgenic mice that expressed the human interleukin-2 receptor (hIL-2R)/GFP fusion protein under the control of the mGluR2 promoter. The immunotoxin that was composed of the monoclonal hIL-2R antibody fused to bacterial toxin was injected into the striatum. Immunotoxin injection selectively eliminated cholinergic interneurons in the basal ganglia network. Unilateral ablation of cholinergic neurons caused an acute abnormal turning and showed a gradual recovery thereafter. This recovery was incomplete and displayed abnormal turning by excess stimulation and inhibition of dopamine. In the acute phase, the reduction of basal ganglia acetylcholine resulted in a predominant action of dopamine. D1 and D2 dopamine receptors were then down-regulated, thus relieving dopamine overactions and compensating acetylcholine-depleted synaptic perturbation. However, this compensation was still defective in responding to excess stimulation and inhibition of dopamine. Therefore, the acetylcholine-dopamine interaction is concertedly and adaptively regulated in basal ganglia function. We also investigated the role of acetylcholine in the nucleus accumbens by bilaterally ablating cholinergic neurons from the nucleus accumbens. Bilateral cholinergic cell elimination markedly enhanced reinforcement and addiction of cocaine and morphine. Acetylcholine in the nucleus accumbens is critical in controlling neural plasticity associated with abuse of drugs.

Parvalbumin (PV) is expressed in fast-twitch fibers in skeletal muscles and a subpopulation of inhibitory neurons in the CNS. We generated transgenic mice that expressed the human interleukin-2 receptor alpha-subunit-green fluorescent fusion protein (hIL-2R-GFP) using two types of PV transgene. One contained the hIL-2R-GFP gene downstream of a 16.5-kb 5'-upstream PV genomic sequence (PV line). The other comprised the hIL-2R-GFP gene in bacterial artificial chromosome (BAC) with either a 180-kb (PA line) or 155-kb (PB line) insert encompassing the PV gene. Independent lines of all transgenic mice showed a faithful hIL-2R-GFP expression in fast-twitch muscle fibers. However, appreciable hIL-2R-GFP expression in the CNS occurred only in the PA transgenic lines. In one line of PA transgenic mice, hIL-2R-GFP was properly expressed in PV-containing neurons in the cerebellum, thalamic reticular nucleus, globus pallidus and cerebral cortex, though ectopic expression was observed in a particular subset of cerebellar astrocytes. Another line of PA transgenic mice showed a selective and mosaic expression of hIL-2R-GFP in PV-containing Purkinje, basket and stellate cells in the cerebellum. These results indicate that the 16.5-kb PV genomic sequence is sufficient for fiber-type-selective transcription but additional regulatory sequences comprised in BAC DNA are required for proper expression in PV-containing neurons.

The directional selectivity of retinal ganglion cell responses represents a primitive pattern recognition that operates within a retinal neural circuit. The cellular origin and mechanism of directional selectivity were investigated by selectively eliminating retinal starburst amacrine cells, using immunotoxin-mediated cell targeting techniques. Starburst cell ablation in the adult retina abolished not only directional selectivity of ganglion cell responses but also an optokinetic eye reflex derived by stimulus movement. Starburst cells therefore serve as the key element that discriminates the direction of stimulus movement through integrative synaptic transmission and play a pivotal role in information processing that stabilizes image motion.

The role of inhibitory Golgi cells in cerebellar function was investigated by selectively ablating Golgi cells expressing human interleukin-2 receptor α subunit in transgenic mice, using the immunotoxin-mediated cell targeting technique. Golgi cell disruption caused severe acute motor disorders. These mice showed gradual recovery but retained a continuing inability to perform compound movements. Optical and electrical recordings combined with immunocytological analysis indicated that elimination of Golgi cells not only reduces GABA-mediated inhibition but also attenuates functional NMDA receptors in granule cells. These results demonstrate that synaptic integration involving both GABA inhibition and NMDA receptor activation is essential for compound motor coordination. Furthermore, this integration can adapt after Golgi cell elimination so as not to evoke overexcitation by the reduction of NMDA receptors.

Glutamate receptors are important in neural plasticity, neural development and neurodegeneration. N-methyl-d-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors act as glutamate-gated cation channels, whereas metabotropic receptors (mGluRs) modulate the production of second messengers via G proteins. Molecular studies from our and other laboratories indicated that NMDA receptors and mGluRs exist as multiple subunits (NMDAR1 and NMDAR2A-2D) and multiple subtypes (mGluR1-mGluR8). In light of the molecular diversity of glutamate receptors, we explored the function and intracellular signaling mechanisms of different members of glutamate receptors. In the visual system, retinal bipolar cells receive glutamate transmission from photoreceptors and contribute to segregating visual signals into ON and OFF pathways. The molecularly cloned mGluR6 is restrictedly expressed at the postsynaptic site of ON-bipolar cells in both rod and cone systems. Gene targeting of mGluR6 results in a loss of ON responses without changing OFF responses and severely impairs detecting visual contrasts. Since AMPA receptors mediate OFF responses in OFF-bipolar cells, two distinct types of glutamate receptors effectively operate for ON and OFF responses. mGluR1 and mGluR5 are both coupled to inositol triphosphate (IP3)/calcium signal transduction with an identical agonist selectivity. Single-cell intracellular calcium ([Ca2+]i) recordings indicated that glutamate evokes a non-oscillatory and oscillatory [Ca2+]i response in mGluR1-expressing and mGluR5-expressing cells, respectively. This difference results from a single amino acid substitution, aspartate of mGluR1 or threonine of mGluR5, at the G protein-interacting carboxy-terminal domains. Protein kinase C phosphorylation of the threonine of mGluR5 is responsible for inducing [Ca2+]i oscillations in mGluR5-expressing cells and cultured glial cells. Thus, the two closely related mGluR subtypes mediate diverging intracellular signaling in glutamate transmission.

Niobium oxide films were prepared over a quartz plate by withdrawing it from a solution of niobium penta-isopropoxide (NIP) dissolved in sec-propyl alcohol. The films calcined at 673 K were well controlled in the film thickness either by NIP concentration in the solution or by the withdrawing rate of the quartz plate from the solution. BET surface area of the calcined films was as huge as around 400 m2g−1 and was not reduced by cyclic adsorption/desorption of water vapor. A rapid decrease and increase in the electrical resistivity of the calcined films was well associated with the cyclic adsorption/desorption of water vapor. The decrease in the electrical resistivity of the films by water vapor adsorption was more than 10 times sensitive than the decrease caused by the adsorption of ethanol, hydrocarbons, carbon monoxide and carbon dioxide. These results suggest an application of the niobium oxide films as an element of a humidity sensor. The calcined films were proved by SEM observation to consist of tiny particles possessing a lotofmicropores sized less than 20 A. The decrease in the electrical resistivity of the films, or the increase in the electrical conductivity, was attributed to the water vapor adsorbed in these micropores. In order to identify the charge carriers during water vapor adsorption on the films, changes in the impedance and the phase shift caused by water vapor adsorption were measured using an LCR meter in AC frequency range of 10 Hz to 100 kHz. From a complex impedance plotting, single semicircule was obtained for water vapor adsorption onto the films, suggesting single adsorbed species as a charge carrier. Assuming an equivalent electric circuit for the films adsorbing water vapor, a constant capacitance was calculated under various partial pressures of water vapor, probably suggesting that the charge carriers will be H3O+ on the films.