Publications by authors named "Yasuyuki Yamamoto"

27 Publications

  • Page 1 of 1

The Potential of Neuraminidase as an Antigen for Nasal Vaccines To Increase Cross-Protection against Influenza Viruses.

J Virol 2021 Sep 11;95(20):e0118021. Epub 2021 Aug 11.

Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.

Despite the availability of vaccines that efficiently reduce the severity of clinical symptoms, influenza viruses still cause substantial morbidity and mortality worldwide. In this regard, nasal influenza vaccines-because they induce virus-specific IgA-may be more effective than traditional parenteral formulations in preventing infection of the upper respiratory tract. In addition, the neuraminidase (NA) of influenza virus has shown promise as a vaccine antigen to confer broad cross-protection, in contrast to hemagglutinin (HA), the target of most current vaccines, which undergoes frequent antigenic changes, leading to vaccine ineffectiveness against mismatched heterologous strains. However, the usefulness of NA as an antigen for nasal vaccines is unclear. Here, we compared NA and HA as antigens for nasal vaccines in mice. Intranasal immunization with recombinant NA (rNA) plus adjuvant protected mice against not only homologous but also heterologous virus challenge in the upper respiratory tract, whereas intranasal immunization with rHA failed to protect against heterologous challenge. In addition, intranasal immunization with rNA, but not rHA, conferred cross-protection even in the absence of adjuvant in virus infection-experienced mice; this strong cross-protection was due to the broader capacity of NA-specific antibodies to bind to heterologous virus. Furthermore, the NA-specific IgA in the upper respiratory tract that was induced through rNA intranasal immunization recognized more epitopes than did the NA-specific IgG and IgA in plasma, again increasing cross-protection. Together, our findings suggest the potential of NA as an antigen for nasal vaccines to provide broad cross-protection against both homologous and heterologous influenza viruses. Because mismatch between vaccine strains and epidemic strains cannot always be avoided, the development of influenza vaccines that induce broad cross-protection against antigenically mismatched heterologous strains is needed. Although the importance of NA-specific antibodies to cross-protection in humans and experimental animals is becoming clear, the potential of NA as an antigen for providing cross-protection through nasal vaccines is unknown. We show here that intranasal immunization with NA confers broad cross-protection in the upper respiratory tract, where virus transmission is initiated, by inducing NA-specific IgA that recognizes a wide range of epitopes. These data shed new light on NA-based nasal vaccines as powerful anti-influenza tools that confer broad cross-protection.
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http://dx.doi.org/10.1128/JVI.01180-21DOI Listing
September 2021

Damage-free light-induced assembly of intestinal bacteria with a bubble-mimetic substrate.

Commun Biol 2021 03 22;4(1):385. Epub 2021 Mar 22.

Department of Physical Science, Graduate School of Science, Osaka Prefecture University, Osaka, Japan.

Rapid evaluation of functions in densely assembled bacteria is a crucial issue in the efficient study of symbiotic mechanisms. If the interaction between many living microbes can be controlled and accelerated via remote assembly, a cultivation process requiring a few days can be ommitted, thus leading to a reduction in the time needed to analyze the bacterial functions. Here, we show the rapid, damage-free, and extremely dense light-induced assembly of microbes over a submillimeter area with the "bubble-mimetic substrate (BMS)". In particular, we successfully assembled 10-10 cells of lactic acid bacteria (Lactobacillus casei), achieving a survival rate higher than 95% within a few minutes without cultivation process. This type of light-induced assembly on substrates like BMS, with the maintenance of the inherent functions of various biological samples, can pave the way for the development of innovative methods for rapid and highly efficient analysis of functions in a variety of microbes.
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http://dx.doi.org/10.1038/s42003-021-01807-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985151PMC
March 2021

Sensorless Self-Excited Vibrational Viscometer with Two Hopf Bifurcations Based on a Piezoelectric Device.

Sensors (Basel) 2021 Feb 5;21(4). Epub 2021 Feb 5.

Device Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8564, Japan.

In this study, we propose a high-sensitivity sensorless viscometer based on a piezoelectric device. Viscosity is an essential parameter frequently used in many fields. The vibration type viscometer based on self-excited oscillation generally requires displacement sensor although they can measure high viscosity without deterioration of sensitivity. The proposed viscometer utilizes the sensorless self-excited oscillation without any detection of the displacement of the cantilever, which uses the interaction between the mechanical dynamics of the cantilever and the electrical dynamics of the piezoelectric device attached to the cantilever. Since the proposed viscometer has fourth-order dynamics and two coupled oscillator systems, the systems can produce different self-excited oscillations through different Hopf bifurcations. We theoretically showed that the response frequency jumps at the two Hopf bifurcation points and this distance between them depends on the viscosity. Using this distance makes measurement highly sensitive and easier because the jump in the response frequency can be easily detected. We experimentally demonstrate the efficiency of the proposed sensorless viscometer by a macro-scale measurement system. The results show the sensitivity of the proposed method is higher than that of the previous method based on self-excited oscillation with a displacement sensor.
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http://dx.doi.org/10.3390/s21041127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914412PMC
February 2021

Vaccine effect of recombinant single-chain hemagglutinin protein as an antigen.

Heliyon 2020 Jun 27;6(6):e04301. Epub 2020 Jun 27.

Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.

Vaccination is one of the most effective interventions for preventing the spread of influenza viruses at the population level. Currently most influenza vaccines are produced by using embryonated chicken eggs, but alternative methods that achieve more rapid large-scale production are highly desirable for vaccines against both pandemic and seasonal influenza viruses. The use of recombinant hemagglutinin (HA), a key virus surface protein, as an antigen is an attractive candidate alternative approach, because of the potential for high protein yields and the ease of cloning new antigenic variants. Although fusion of HA with trimerization domains is needed to stabilize the trimeric structure and enhance the immunogenicity of the recombinant HA protein, whether the trimerization domains are immunogenic must be considered. Here, we generated recombinant multimeric HA without trimerization domains by using a short peptide linker, termed a single-chain HA (scHA), and evaluated scHAs as potential antigens for generating vaccines against influenza virus. Using mammalian cells, we succeeded in making three types of recombinant scHAs-two dimeric scHAs and a trimeric scHA. After immunization with aluminium salts in mice, one of the dimeric scHAs induced the greatest HA-specific IgG response among the scHAs and protected against virus challenge as strongly as the typically used trimeric HA containing a trimerization domain. We did not observe IgGs specific for the short peptide linker in mice immunized with the dimeric scHA, although IgGs specific for the trimerization domain occurred in mice immunized with the trimeric HA containing that domain. Furthermore, changing to another adjuvant did not diminish the utility of the dimeric scHA. These results suggest the potential usefulness of dimeric scHA as a vaccine antigen. We believe that single-chain antigens may represent new alternatives for production of recombinant antigen-based vaccines.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327749PMC
June 2020

Ultra-Sensitive Minute Mass Sensing Using a Microcantilever Virtually Coupled with a Virtual Cantilever.

Sensors (Basel) 2020 Mar 25;20(7). Epub 2020 Mar 25.

Research Center for Ubiquitous MEMS and Micro Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8564, Japan.

Mass sensors based on the eigenmode shift of coupled cantilevers achieve much higher sensitivity than those based on the single cantilever's eigenfrequency shift. In the former sensors, two identical cantilevers and a weak coupling stiffness between them are required to achieve high sensitivity. However, conventional coupled cantilevers cannot satisfy these requirements because of machining accuracy. To satisfy both requirements, a virtual coupling between a real macrocantilever and a virtual cantilever, whose dynamics was calculated using a digital computer, was proposed in our previous research. The sensitive mass sensing of mg-order masses was achieved. In the present work, for minute mass sensing, we replace the real macrocantilever with a real microcantilever. The calculation speed of a digital computer is not fast enough to calculate the virtual cantilever's dynamics because the natural frequency of the microcantilver is much higher than that of the macrocantilever. Therefore, we use an analog circuit instead of a digital computer to achieve virtual coupling with the virtual cantilever. The proposed system enables us to tune the virtual cantilever's parameters to satisfy both requirements for high sensitivity by changing the analog circuit parameters. We verified experimentally that the proposed system achieved high sensitivity for mass sensing of the order of nanograms.
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http://dx.doi.org/10.3390/s20071823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180872PMC
March 2020

Light-induced assembly of living bacteria with honeycomb substrate.

Sci Adv 2020 02 28;6(9):eaaz5757. Epub 2020 Feb 28.

Research Institute for Light-induced Acceleration System, Osaka Prefecture University, Sakai 599-8570, Japan.

Some bacteria are recognized to produce useful substances and electric currents, offering a promising solution to environmental and energy problems. However, applications of high-performance microbial devices require a method to accumulate living bacteria into a higher-density condition in larger substrates. Here, we propose a method for the high-density assembly of bacteria (10 to 10 cells/cm) with a high survival rate of 80 to 90% using laser-induced convection onto a self-organized honeycomb-like photothermal film. Furthermore, the electricity-producing bacteria can be optically assembled, and the electrical current can be increased by one to two orders of magnitude simply by increasing the number of laser irradiations. This concept can facilitate the development of high-density microbial energy conversion devices and provide new platforms for unconventional environmental technology.
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http://dx.doi.org/10.1126/sciadv.aaz5757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048417PMC
February 2020

Measurement of Heat Dissipation and Thermal-Stability of Power Modules on DBC Substrates with Various Ceramics by SiC Micro-Heater Chip System and Ag Sinter Joining.

Micromachines (Basel) 2019 Oct 31;10(11). Epub 2019 Oct 31.

The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.

This study introduced the SiC micro-heater chip as a novel thermal evaluation device for next-generation power modules and to evaluate the heat resistant performance of direct bonded copper (DBC) substrate with aluminum nitride (AlN-DBC), aluminum oxide (DBC-AlO) and silicon nitride (SiN-DBC) ceramics middle layer. The SiC micro-heater chips were structurally sound bonded on the two types of DBC substrates by Ag sinter paste and Au wire was used to interconnect the SiC and DBC substrate. The SiC micro-heater chip power modules were fixed on a water-cooling plate by a thermal interface material (TIM), a steady-state thermal resistance measurement and a power cycling test were successfully conducted. As a result, the thermal resistance of the SiC micro-heater chip power modules on the DBC-AlO substrate at power over 200 W was about twice higher than DBC-SiN and also higher than DBC-AlN. In addition, during the power cycle test, DBC-AlO was stopped after 1000 cycles due to Pt heater pattern line was partially broken induced by the excessive rise in thermal resistance, but DBC-SiN and DBC-AlN specimens were subjected to more than 20,000 cycles and not noticeable physical failure was found in both of the SiC chip and DBC substrates by a x-ray observation. The results indicated that AlN-DBC can be as an optimization substrate for the best heat dissipation/durability in wide band-gap (WBG) power devices. Our results provide an important index for industries demanding higher power and temperature power electronics.
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http://dx.doi.org/10.3390/mi10110745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915596PMC
October 2019

The TK0271 Protein Activates Transcription of Aromatic Amino Acid Biosynthesis Genes in the Hyperthermophilic Archaeon Thermococcus kodakarensis.

mBio 2019 09 10;10(5). Epub 2019 Sep 10.

Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, Japan

TrpY from is a regulator that inhibits transcription of the Trp biosynthesis () operon. Here, we show that the TrpY homolog in is not involved in such regulation. There are 87 genes on the genome predicted to encode transcriptional regulators (TRs). By screening for TRs that specifically bind to the promoter of the operon of , we identified TK0271. The gene resides in the operon, responsible for the biosynthesis of chorismate, a precursor for Trp, Tyr, and Phe. TK0271 was expressed in , and the protein, here designated Tar ( romatic amino acid egulator), was purified. Tar specifically bound to the promoter with a dissociation constant ( ) value of approximately 5 nM. Tar also bound to the promoters of the Tyr/Phe biosynthesis () and operons. The protein recognized a palindromic sequence (TGGACA-N-TGTCCA) conserved in these promoters. transcription assays indicated that Tar activates transcription from all three promoters. We cultivated in amino acid-based medium and found that transcript levels of the , , and operons increased in the absence of Trp, Tyr, or Phe. We further constructed a TK0271 gene disruption strain (ΔTK0271). Growth of ΔTK0271 was similar to that of the host strain in medium including Trp, Tyr, and Phe but was significantly impaired in the absence of any one of these amino acids. The results suggest that Tar is responsible for the transcriptional activation of aromatic amino acid biosynthesis genes in The mechanisms of transcriptional regulation in archaea are still poorly understood. In this study, we identified a transcriptional regulator in the hyperthermophilic archaeon that activates the transcription of three operons involved in the biosynthesis of aromatic amino acids. The study represents one of only a few that identifies a regulator in that activates transcription. The results also imply that transcriptional regulation of genes with the same function is carried out by diverse mechanisms in the archaea, depending on the lineage.
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http://dx.doi.org/10.1128/mBio.01213-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737238PMC
September 2019

Peptides with the multibasic cleavage site of the hemagglutinin from highly pathogenic influenza viruses act as cell-penetrating via binding to heparan sulfate and neuropilins.

Biochem Biophys Res Commun 2019 05 21;512(3):453-459. Epub 2019 Mar 21.

Vaccine Creation Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; BIKEN Center for Innovative Vaccine Research and Development, The Research Foundation for Microbial Diseases of Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan; Global Center for Medical Engineering and Informatics, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address:

Cell-penetrating peptides (CPPs) show promise as an attractive delivery vehicle for therapeutic molecules-including nucleic acids, peptides, proteins, and even particulates-into several cell types. It is important to identify new CPPs and select the optimal CPP for each application, because CPPs differ in their internalized efficiency and internalization mechanisms. Here, we identified new CPPs derived from the peptides with the hemagglutinin cleavage site (pHACS) of highly pathogenic influenza viruses. We compared the potential of peptides from the pHACS of four subtypes of influenza A virus (H1, H3, H5, and H7) and an influenza B virus (H1-pHACS, H3-pHACS, H5-pHACS, H7-pHACS, and B-pHACS, respectively) to serve as CPPs. H5-pHACS and H7-pHACS, but not the other peptides, bound to mouse dendritic cells and human epithelial cells and were internalized efficiently into these cells. H5-pHACS and H7-pHACS required glycosaminoglycans, especially heparan sulfate and neuropilins, to bind to the cells. In addition, we designed a mutant H7-pHACS with superior cell-binding capability by changing a single amino acid. Furthermore, when conjugated with antigen, H5-pHACS and H7-pHACS induced antigen-specific antibody responses, demonstrating the usefulness of this antigen-delivery vehicle. Our results will improve our understanding of the mechanisms of CPPs and facilitate the development of novel drug-delivery vehicles designed to improve therapeutic efficacy.
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http://dx.doi.org/10.1016/j.bbrc.2019.03.068DOI Listing
May 2019

Macroscopically Anisotropic Structures Produced by Light-induced Solvothermal Assembly of Porphyrin Dimers.

Sci Rep 2018 07 23;8(1):11108. Epub 2018 Jul 23.

Department of Physics, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuencho, Naka-ku, Sakai, Osaka, 599-8531, Japan.

Porphyrin-based molecules play an important role in natural biological systems such as photosynthetic antennae and haemoglobin. Recent organic chemistry provides artificial porphyrin-based molecules having unique electronic and optical properties, which leads to wide applications in material science. Here, we successfully produced many macroscopically anisotropic structures consisting of porphyrin dimers by light-induced solvothermal assembly with smooth evaporation in a confined volatile organic solvent. Light-induced fluid flow around a bubble on a gold nanofilm generated a sub-millimetre radial assembly of the tens-micrometre-sized petal-like structures. The optical properties of the petal-like structures depend on the relative angle between their growth direction and light polarisation, as confirmed by UV-visible extinction and the Raman scattering spectroscopy analyses, being dramatically different from those of structures obtained by natural drying. Thus, our findings pave the way to the production of structures and polycrystals with unique characteristics from various organic molecules.
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http://dx.doi.org/10.1038/s41598-018-28311-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056561PMC
July 2018

Carbonate Apatite Nanoparticles Act as Potent Vaccine Adjuvant Delivery Vehicles by Enhancing Cytokine Production Induced by Encapsulated Cytosine-Phosphate-Guanine Oligodeoxynucleotides.

Front Immunol 2018 18;9:783. Epub 2018 Apr 18.

Vaccine Creation Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.

Vaccine adjuvants that can induce not only antigen-specific antibody responses but also Th1-type immune responses and CD8 cytotoxic T lymphocyte responses are needed for the development of vaccines against infectious diseases and cancer. Of many available adjuvants, oligodeoxynucleotides (ODNs) with unmethylated cytosine-phosphate-guanine (CpG) motifs are the most promising for inducing the necessary immune responses, and these adjuvants are currently under clinical trials in humans. However, the development of novel delivery vehicles that enhance the adjuvant effects of CpG ODNs, subsequently increasing the production of cytokines such as type-I interferons (IFNs), is highly desirable. In this study, we demonstrate the potential of pH-responsive biodegradable carbonate apatite (CA) nanoparticles as CpG ODN delivery vehicles that can enhance the production of type-I IFNs (such as IFN-α) relative to that induced by CpG ODNs and can augment the adjuvant effects of CpG ODNs . In contrast to CpG ODNs, CA nanoparticles containing CpG ODNs (designated CA-CpG) induced significant IFN-α production by mouse dendritic cells and human peripheral blood mononuclear cells ; and production of interleukin-12, and IFN-γ was higher in CA-CpG-treated groups than in CpG ODNs groups. In addition, treatment with CA-CpG resulted in higher cytokine production in draining lymph nodes than did treatment with CpG ODNs . Furthermore, vaccination with CA-CpG plus an antigen, such as ovalbumin or influenza virus hemagglutinin, resulted in higher antigen-specific antibody responses and CD8 cytotoxic T lymphocyte responses , in an interleukin-12- and type-I IFN-dependent manner, than did vaccination with the antigen plus CpG ODNs; in addition, the efficacy of the vaccine against influenza virus was higher with CA-CpG as the adjuvant than with CpG ODNs as the adjuvant. These data show the potential of CA nanoparticles to serve as CpG ODN delivery vehicles that increase the production of cytokines, especially IFN-α, induced by CpG ODNs and thus augment the efficacy of CpG ODNs as adjuvants. We expect that the strategy reported herein will facilitate the design and development of novel adjuvant delivery vehicles for vaccines.
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http://dx.doi.org/10.3389/fimmu.2018.00783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916113PMC
June 2019

Engineering of the Hyperthermophilic Archaeon Thermococcus kodakarensis for Chitin-Dependent Hydrogen Production.

Appl Environ Microbiol 2017 Aug 17;83(15). Epub 2017 Jul 17.

Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan

is a hyperthermophilic archaeon that harbors a complete set of genes for chitin degradation to fructose 6-phosphate. However, wild-type KOD1 does not display growth on chitin. In this study, we developed a strain that can grow on chitin via genetic and adaptive engineering. First, a chitinase overproduction strain (KC01) was constructed by replacing the chitinase gene promoter with a strong promoter from the cell surface glycoprotein gene, resulting in increased degradation of swollen chitin and accumulation of -,'-diacetylchitobiose in the medium. To enhance -,'-diacetylchitobiose assimilation in KC01, genes encoding diacetylchitobiose deacetylase, exo-β-d-glucosaminidase, and glucosamine-6-phosphate deaminase were also overexpressed to obtain strain KC04. To strengthen the glycolytic flux of KC04, the gene encoding Tgr (transcriptional repressor of glycolytic genes) was disrupted to obtain strain KC04Δt. In both KC04 and KC04Δt strains, degradation of swollen chitin was further enhanced. In the culture broth of these strains, the accumulation of glucosamine was observed. KC04Δt was repeatedly inoculated in a swollen-chitin-containing medium for 13 cultures. This adaptive engineering strategy resulted in the isolation of a strain (KC04ΔtM1) that showed almost complete degradation of 0.4% (wt/vol) swollen chitin after 90 h. The strain produced high levels of acetate and ammonium in the culture medium, and, moreover, molecular hydrogen was generated. This strongly suggests that strain KC04ΔtM1 has acquired the ability to convert chitin to fructose 6-phosphate via deacetylation and deamination and further convert fructose 6-phosphate to acetate via glycolysis coupled to hydrogen generation. Chitin is a linear homopolymer of β-1,4-linked -acetylglucosamine and is the second most abundant biomass next to cellulose. Compared to the wealth of research focused on the microbial degradation and conversion of cellulose, studies addressing microbial chitin utilization are still limited. In this study, using the hyperthermophilic archaeon as a host, we have constructed a strain that displays chitin-dependent hydrogen generation. The apparent hydrogen yield per unit of sugar consumed was slightly higher with swollen chitin than with starch. As gene manipulation in is relatively simple, the strain constructed in this study can also be used as a parent strain for the development and expansion of chitin-dependent biorefinery, in addition to its capacity to produce hydrogen.
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http://dx.doi.org/10.1128/AEM.00280-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514669PMC
August 2017

[Investigation of the Pathophysiology and Diagnostic Methods Through a Case of Acute HIV Infection in which the Western Blot Method Remained Negative Over the Long Term and the 4th Generation Screening Assay Became Negative for a Certain Period of Time after Initiating Antiretroviral Therapy].

Kansenshogaku Zasshi 2017 Jan;91(1):7-12

Confirmatory tests using Western blot (WB) and HIV-1 nucleic acid testing (HIV-1 RNA) following a positive screening test are required for the diagnosis of HIV-1 infection according to the current Japanese guidelines for HIV-1/2 diagnosis. We report herein on a rare case in a patient who remained negative for WB over 10 months in spite of being positive by fourth-generation immunoassays (4thGIA) and who subsequently seroreverted by 4thGIA for three months after initiating antiretroviral therapy.

Case: A man in his early twenties previously visited a hospital because of fever in October 2012. Laboratory data revealed leukocytopenia, thrombocytopenia and increased serum ferritin, suggesting hemophagocytic syndrome (HPS). During that visit, he tested positive for a 4thGIA, but negative for HIV-1 WB and his result of HIV-1 RNA result was detected invalid because of the presence of some inhibitory material in his RNA preparation. Thereafter, he was diagnosed as having cytomegalovirus-associated HPS treatment was for which initiated. In January 2013, he developed Pneumocystis jirovecii pneumonia, and his HIV-1 RNA viral load was 7.7 × 105 copies/mL in February 2013. Acute HIV infection was suspected, because the HIV-1 WB remained negative. He was started on antiretroviral therapy in April 2013. His 4thGIA was converted to negative in May 2013 and was reconverted to positive in August 2013. HIV-1 WB, however, continued to be indeterminant until February 2014, in which it turned positive for the first time according to the CDC criteria.

Methods And Results: The genetic analyses of HIV-1 were done on the gag, env, nef and pol region of the HIV-1 gene from the patient. There was no clear element to delay antibody production on the virus side. Preserved specimens of the patient were measured with eight kinds of HIV screening assay. It was thought that the fourth generation assay was positive only by the presence of the antigen until March 2013 because the antibody had not been detected.

Discussion: We encountered a case of acute HIV infection in which the WB result was negative for 10 months after the first positive response of the 4thGIA. The 4thGIA is essential for the early diagnosis and early treatment of HIV infection; therefore, the 4thGIA should be strictly recommended to avoid the use of older generations of immunoassay in the diagnostic guidelines. The role of the WB test should be examined closely from various aspects for use as a confirmatory test under recent laboratory situations in which highly sensitive and specific methods, e.g. the 4th GIA, have become available. In addition, unnecessary confusion due to the diversities of antibody formation should be avoided. The antibody detection tests for HIV are still necessary and indispensable for the confirmation of the disease or the diagnosis of the acute infection stage. Therefore development of a newer antibody measuring method which could achieve an easier operation and should have a higher sensitivity and specificity for HIV confirmation is strongly expected.
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January 2017

[Syphilis Testing and High Rate of Infection Among HIV-infected Patients].

Kansenshogaku Zasshi 2016 Nov;90(6):798-802

Background: The incidence of syphilis has globally increased over the last decade, particularly among men who have sex with men coinfected with the human immunodeficiency virus (HIV). HIV infection may make the clinical symptoms and seroreactivity of syphilis atypical, which requires careful consideration in terms of diagnoses and treatments by clinicians. Syphilis is known as a great imitator, and is often difficult to be diagnosed or it can be overlooked if clinicians depend only on its symptoms or signs. It is also highly contagious and could be transmitted without sexual intercourse, and reinfection is common. Guidelines recommend that all HIV-infected persons be provided with STD screening, including syphilis, at least annually. However, to our knowledge, there are no published data on the actual frequency of testing and instances of syphilis among HIV-infected persons in Japan.

Materials And Methods: We collected data from HIV infected male patients who had sex with men (MSM) at Tokyo Medical University Hospital from June 2011 to June 2012. Data from the patients, who had been tested with the rapid plasma reagin assay (RPR) at least once during the study period, were retrospectively obtained from clinical records and were analyzed.

Results: Among 1000 patients with HIV infection, 935 patients were MSM. 723 patients (77.4%) were tested using the Treponema pallidum latex agglutination test (TPLA) and RPR more than once during the study period. Out of the 723 patients, 443 patients (61.3%) were reactive for TPLA and 238 patients (32.9%) had reactive tests for RPR. All patients who were reactive for RPR were reactive for TPLA. Among the patients who were reactive for RPR, 93 patients (12.9%) were considered newly diagnosed or with a repeat infection. In this cohort, all patients were MSM with a median age of 37 years, and a median CD4+T-lymphocyte cell count of 465/uL. A total of 76 patients had been prescribed antiretroviral therapy, and 61 patients had a documented HIV-1 RNA viral load of <40 copies/mL at their most recent test. Two patients both developed two episodes of syphilis during the study period. Of the 95 episodes, 44% were symptomatic syphilis and the most common symptom among them was a skin rash at the second stage. Nearly half of the patients (47%) were diagnosed at regular screenings. Two thirds (67%) had syphilis infections before the study period, whereas at least 20% of them were newly diagnosed during the study period.

Conclusions: A substantial percentage of the participants were newly or recurrently diagnosed with syphilis during the study period. More public health awareness should be encouraged regarding the current epidemic of syphilis among HIV-infected persons in Japan. It is also important for clinicians to provide HIV-infected persons with periodical syphilis screening, regardless of the apparent clinical signs or symptoms to achieve earlier treatment intervention.
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November 2016

The Prevalence of High Antiretroviral Coverage and Viral Suppression in Japan: an Excellent Profile for a Downstream Human Immunodeficiency Virus Care Spectrum.

Jpn J Infect Dis 2017 Mar 30;70(2):158-160. Epub 2016 Jun 30.

The Institute of Medical Science, The University of Tokyo.

We investigated the effectiveness of the Japanese health care system for human immunodeficiency virus/acquired immunodeficiency virus (HIV/AIDS), in terms of prevention, diagnosis, access to antiretroviral treatment, and treatment outcomes. Clinical information on HIV/AIDS cases was collected via questionnaires sent to 377 registered HIV/AIDS clinics in Japan. Data on 9,040 and 14,569 cases were collected in 2009 and 2014, respectively. The percentages of cases undergoing treatment were 69.6% and 87.8% in 2009 and 2014, respectively, demonstrating an improvement in treatment coverage over the 5 years between the 2 surveys. The proportion of cases with undetectable HIV RNA in the 2014 survey was 87.7%. Thus, our survey revealed that the 2 of the United Nations AIDS Fast-Track targets, 90% treated and 90% virally suppressed, are close to being achieved. However, Japan appears to have fallen short of the upstream target of 90% diagnosed. Japan needs to radically reform its strategies for encouraging people to undergo HIV testing and to develop a system for estimating the number of people living with HIV.
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http://dx.doi.org/10.7883/yoken.JJID.2015.599DOI Listing
March 2017

A high performance photothermal film with spherical shell-type metallic nanocomposites for solar thermoelectric conversion.

Nanoscale 2015 May;7(17):7580-4

Nanoscience and Nanotechnology Research Center, Osaka Prefecture University, Sakai 599-8570, Japan.

A photothermal film (PTF) with densely assembled gold nanoparticle-fixed beads on a polymer substrate is fabricated. Remarkably, a temperature rise higher than 40 °C is achieved in the PTF with only 100 seconds of artificial solar irradiation, and the output power of the thermoelectric device was enhanced to be one order higher than that without PTF. These results will pioneer a rapid solar thermoelectric device.
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http://dx.doi.org/10.1039/c5nr00943jDOI Listing
May 2015

Ruthenium sensitizers with a hexylthiophene-modified terpyridine ligand for dye-sensitized solar cells: synthesis, photo- and electrochemical properties, and adsorption behavior to the TiO2 surface.

ACS Appl Mater Interfaces 2015 Feb 27;7(5):3152-61. Epub 2015 Jan 27.

Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science , 12-1, Ichigaya-Funagawara, Shinjuku, Tokyo, 162-0826, Japan.

Two novel ruthenium sensitizers with a hexylthiophene-modified terpyridine ligand (TUS-35 and TUS-36) were synthesized to improve the molar absorptivity of the previously reported ruthenium sensitizer (TBA)[Ru{4'-(3,4-dicarboxyphenyl)-4,4″-dicarboxyterpyridine}(NCS)3], TBA = tetrabutylammonium (TUS-21). A relatively strong absorption appeared at ∼380 nm, and the molar absorption coefficient at the metal-to-ligand charge transfer (MLCT) band decreased in TUS-35 by introducing a 2-hexylthiophene unit to the 5-position of the terpyridine-derived ligand. For comparison, a relatively strong absorption was observed at ∼350 nm without decreasing the molar absorption coefficient at the MLCT band in TUS-36 by introducing a 2-hexylthiophene unit to the 4-position of the terpyridine-derived ligand. On the other hand, the energy levels of the highest occupied molecular orbitals and the lowest unoccupied molecular orbitals of these two sensitizers were found to be almost equal to those of TUS-21. The adsorption behavior of TUS-35 and TUS-36 was similar to that of (TBA)[Ru{4'-(3,4-dicarboxyphenyl)terpyridine}(NCS)3] (TUS-20), which binds to the TiO2 surface by using the 3,4-dicarboxyphenly unit, rather than that of TUS-21, which adsorbs to the TiO2 photoelectrode using one of the carboxyl groups at the terminal pyridines of the terpyridine-derived ligand. Therefore, TUS-35 and TUS-36 are considered to bind to the TiO2 surface by using the 3,4-dicarboxyphenly unit just like TUS-20. The dye-sensitized solar cells (DSCs) with TUS-35 and TUS-36 showed a relatively lower conversion efficiency (6.4% and 5.7%, respectively) compared to the DSC with TUS-21 (10.2%). Open-circuit photovoltage decay and electrochemical impedance spectroscopy measurements revealed that the promoted charge recombination and/or charge transfer of the injected electrons in the TiO2 photoelectrode is a main reason for the inferior performances of TUS-35 and TUS-36.
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http://dx.doi.org/10.1021/am507442sDOI Listing
February 2015

Subjective adverse reactions to metronidazole in patients with amebiasis.

Parasitol Int 2014 Oct 12;63(5):698-700. Epub 2014 Jun 12.

Department of Infectious Diseases, National Hospital Organization Osaka National Hospital, Osaka 540-0006, Japan.

Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea.
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http://dx.doi.org/10.1016/j.parint.2014.05.006DOI Listing
October 2014

[Status of use and side effects of atovaquone for the treatment and prevention of pneumocystis pneumonia in HIV infected patients in Japan--from 1997 to 2012--The Clinical Study Group for AIDS Drugs, supported by Health and Labor Science Grants from the Ministry of Health, Labor and Welfare, Japan].

Kansenshogaku Zasshi 2013 Jul;87(4):435-40

Department of Laboratory Medicine, Tokyo Medical University.

Purpose: Atovaquone is effective and well-tolerated for the treatment of mild or moderate Pneumocystis pneumonia (PCP) and the prevention of PCP. When atovaquone was not yet approved in Japan, it was supplied by the Clinical Study Group for AIDS Drugs, which has been supported by the Japan Health Science Foundation since 1997. We investigated the status of use and the reported side effects, since atovaquone has recently been approved and made available in Japan.

Method: We retrospectively examined the application and adverse events associated with atovaquone use between January 1997 and March 2012.

Results: During this period, there were 721 new applications, increasing over time, with the highest rate of increase observed in recent years. Fifty-seven adverse events in 39 patients were reported. Drug eruption was the most common side effect (20 cases), followed by cytopenia (11 cases), fever (10 cases), and liver dysfunction (8 cases). Two deaths were reported (one with an unknown correlation, another with no comments provided). One case of liver dysfunction attributable to atovaquone was severe. In this case, the AST and ALT levels increased to 1,921 IU/L, and 1,062 IU/L, respectively on day 4 of atovaquone administration, but these levels improved after atovaquone discontinuation. No other severe side effects were reported.

Discussion: This study revealed that as in other countries, few side effects caused by atovaquone were reported in Japan. Moreover, there were no side effects unique to the Japanese population. However, caution is required when administering atovaquone, because a low incidence of severe atovaquone-induced liver dysfunction has been reported.
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http://dx.doi.org/10.11150/kansenshogakuzasshi.87.435DOI Listing
July 2013

Classification of human immunodeficiency virus-infected patients with chronic kidney disease using a combination of proteinuria and estimated glomerular filtration rate.

Clin Exp Nephrol 2014 Aug 17;18(4):600-5. Epub 2013 Aug 17.

Department of Infectious Diseases, Tokyo Metropolitan Komagome Hospital, Bunkyo-Ku, Japan.

Background: In 2012, the Kidney Disease: Improving Global Outcomes (KDIGO) updated the 2002 Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guideline for chronic kidney disease (CKD). The 2012 KDIGO guideline elaborated the identification and prognosis of CKD by combining albuminuria with estimated glomerular filtration rate (eGFR). Identification of CKD with a high risk for a poor prognosis was investigated in human immunodeficiency virus (HIV)-infected individuals by applying the new guideline.

Methods: A total of 1,447 HIV-infected patients (1,351 male, 96 female; mean age 44.4 ± 11.5 years) were classified using a combination of eGFR and dipstick proteinuria, as a convenient alternative to albuminuria. Proteinuria was classified into 3 grades-(A1) - and +/- , (A2) 1+ and 2+ , and (A3) 3+ and 4+. eGFR was classified into 6 grades-(G1) ≤90, (G2) 60-89, (G3a) 45-59, (G3b) 30-44, (G4) 15-29, and (G5) <15 mL/min/1.73 m(2).

Results: Mean CD4 cell count was 487 ± 214 /μL, with 80.7 % of patients having an undetectable HIV-RNA level. The prevalence of CKD stage ≤2 and stage ≥3 classified according to KDOQI staging was 93.4 and 6.6 %, respectively. Using the new KDIGO classification, the prevalence of CKD with either a low (green) or moderately increased (yellow) risk was 96.9 %, while the prevalence for a high (orange) and very high (red) risk was 3.1 %.

Conclusion: The use of the new KDIGO classification may reduce the prevalence of HIV-infected CKD individuals who are at high risk for a poor prognosis by nearly a half.
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http://dx.doi.org/10.1007/s10157-013-0853-1DOI Listing
August 2014

[Prevalence of chronic kidney disease among HIV-infected individuals in Japan--a report from two tertiary hospitals].

Kansenshogaku Zasshi 2013 Jan;87(1):14-21

Department of Laboratory Medicine, Tokyo Medical University.

Background: The improved survival of subjects with human immunodeficiency virus (HIV) has been accompanied by an increased prevalence of chronic kidney disease (CKD). Epidemic of CKD among those with HIV has not yet been evaluated in multiple tertiary hospitals in Japan.

Methods: A cross-sectional study was conducted in 2011 at Tokyo Metropolitan Komagome Hospital (TMKH) and Tokyo Medical University Hospital (TMUH). A total of 1482 HIV-infected subjects (1384 men, 98 female, mean age: 44.2 +/- 11.4 years old) were consecutively enrolled in the study. Random urine and blood samples were collected to study prevalence of CKD. CKD was diagnosed as a decrease in glomerular function and/or proteinuria and classified into 5 stages based on National Kidney Foundation guidelines. The estimated glomerular filtration rate based on serum creatinine was calculated using the 3-variable equation, constructed by the Japanese Society of Nephrology. Proteinuria was defined as > or = 1+ on urine dipstick examination. All electronic medical charts were reviewed to determine comorbidities, including hypertension and diabetes mellitus (DM). The proportion of subjects receiving tenofovir disoproxil fumarate (TDF) was investigated. Risk factors for CKD were determined using multivariate logistic regression analysis.

Results: The mean CD4 cell count was 487 +/- 216/microL and 80.5% had undetectable HIV-RNA level in the combined cohort. Of the 90.2% of subjects taking antiretroviral agents, 61.5% was using TDF. The prevalence of overall CKD and CKD > or = stage 3 was 12.9% and 6.7%, respectively, both of which were nearly 3-fold higher in the TMKH cohort (p < .0001). Mean age and proportional prevalent hypertension and DM were significantly higher in the TKMH cohort than in the TMUH cohort. Multivariate analysis showed significant CKD to be associated with age > or =50 years (odds ratio [OR], 2.81), hypertension (OR, 3.04), and DM (OR, 2.05).

Conclusions: CKD prevalence was 12.9% among combined cohorts, but differed significantly between them. Differences in age distribution and the proportion of comorbidities, including hypertension and DM, are likely involved.
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http://dx.doi.org/10.11150/kansenshogakuzasshi.87.14DOI Listing
January 2013

Mutations to the probe of Cobas TaqMan HIV-1 ver. 1.0 assay causing undetectable viral load in a patient with acute HIV-1 infection.

J Infect Chemother 2011 Dec 14;17(6):863-5. Epub 2011 Jun 14.

Department of Laboratory Medicine, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.

We encountered a human immunodeficiency virus (HIV)-1 in which the viral load was undetectable with the Cobas TaqMan HIV-1 ver. 1.0 (CTM v.1.0) in a patient with acute HIV-1 infection. The CTM v.1.0 assay showed more than 1,000-fold underestimation compared with the subsequent Cobas Amplicor Monitor v.1.5 assay. Because five mismatches to the CTM v.1.0 assay probe in the HIV-1 virus in the patient were disclosed by the manufacturer, partial gag regions of the HIV genome were directly sequenced from the patient's plasma viral RNA. The detected single nucleotide point mutations were located near the 5'-end of the Cobas Amplicor Monitor probe. Clinicians should be very careful in making interpretations when indeterminate Western blot analysis results and a low or even undetectable HIV-1 viral load are encountered with the CTM HIV-1 ver. 1.0 assay in patients with suspected acute HIV infection. Repeating Western blot analysis is essential before considering a low HIV-1 viral load to be a false-positive result.
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http://dx.doi.org/10.1007/s10156-011-0263-9DOI Listing
December 2011

Investigation of emtricitabine-associated skin pigmentation and safety in HIV-1-infected Japanese patients.

J Infect Chemother 2011 Oct 3;17(5):602-8. Epub 2011 Mar 3.

AIDS Medical Center, Osaka National Hospital, National Health Organization, 2-1-14 Hoenzaka, Chuo-ku, Osaka 540-0006, Japan.

Emtricitabine (FTC) has been reported to cause skin pigmentation (SP), and the incidence of SP associated with FTC varied with ethnicity, with a higher rate in African-American patients (8%). We assessed the incidence of SP in Japanese HIV-1-infected patients receiving combination antiretroviral therapy (cART) with FTC for a period of 48 weeks and confirmed new findings of FTC-associated SP, including pathological characteristics. This was a multicenter, prospective, longitudinal non-randomized study. We evaluated the appearance of SP at 48 weeks as the primary endpoint in 155 Japanese patients, and secondary endpoints included the characteristics of the SP (location, color tone, size, and progression). Six cases (3.9%) of SP occurred at a median of 124 days (range: 7-259 days) within 48 weeks. The SP looked like an isolated dark spot, 1-2 mm in diameter, mainly on the hands and/or feet. The severity of all the SPs was mild. Each SP had disappeared or faded at a median of 112 days (range: 28-315 days) with continued FTC. FTC-associated SP was considered to be lentigo simplex by dermatoscopy and pathological appearance. In summary, the incidence of FTC-associated SP in Japanese patients was 3.9%, and was comparable to the previously reported incidence in Asian patients (4%). FTC-associated SP was not associated with any clinically significant symptoms and has little clinical significance.
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http://dx.doi.org/10.1007/s10156-011-0222-5DOI Listing
October 2011

[Utilities and limitations of a real-time PCR based assay for HIV-1 RNA quantification].

Rinsho Byori 2010 Feb;58(2):124-30

Objective: This study evaluated the clinical utilities and limitations of HIV 1 RNA quantification using a real time PCR based assay, COBAS AmpliPrep/COBAS Taqman HIV 1 Test(TaqMan), since higher viral loads or wider fluctuations in viral loads have been demonstrated after this assay replaced COBAS AmpliPrep/AMPLICOR HIV-1 Monitor Version 1.5 Ultrasensitive (AMPLICOR).

Design And Results: We conducted a clinical study analyzing HIV-1 RNA levels measured by AMPLICOR assay and by TaqMan assay, CD4+ lymphocyte counts (CD4) and regimens of highly active antiretroviral therapy among patients who were treated in Tokyo Medical University Hospital. HIV 1 RNA levels were measured by an independent clinical laboratory (SRL, Inc.) outside the hospital. More than 50 copies/ml of HIV-1 RNA were demonstrated by TaqMan assay in 47% of 58 specimens in which HIV 1 RNA levels were undetectable (< 50 copies/ml) by AMPLICOR assay. TaqMan assay showed higher levels of HIV-1 RNA in comparison with AMPLICOR assay on correlation analysis. However, there was no tendency toward deterioration of either the serum HIV-1 RNA load or CD4 in patients showing discrepancies between the two assays. There was no correlation between the detection of HIV-1 RNA and the use of certain antiretroviral agents. Repeated assay of specimens from the same collection tube showed large discrepancies.

Conclusion: HIV 1 RNA quantification assay is essential to monitor the effects of antiretroviral therapy. Physicians must remain aware that the TaqMan assay is not yet sufficiently reliable.
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February 2010

Systolic dysfunction in urban Japan.

Circ J 2008 Mar;72(3):349-57

Division of Cardiology, First Department of Internal Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: Heart failure (HF), which can be caused by left ventricular systolic dysfunction (LVSD), is a growing problem in developed countries with a large aging population. The aim of the present study was to characterize outpatients with LVSD in the adult population (45-84 years) in an urban Japanese community (Niigata City), and delineate their characteristics in comparison with those in a rural one (Sado).

Methods And Results: Over a 5-year period, 1,297 patients (67% males) with LVSD (defined as ejection fraction < or =50%) were extracted from 87,953 echocardiography records available in 15 hospitals in Niigata City. The proportion of LVSD increased progressively with age (p-for-trend <0.0001), reaching 1-2% in those aged > or =75 years. The prevalence of comorbidities was noticeable (47% had hypertension, 41% myocardial ischemia, 34% atrial fibrillation, 33% previous hospitalization because of congestive HF, 27% cerebral stroke). In comparison with Sado, Niigata patients were younger, with a higher prevalence of comorbidities (hypertension, diabetes, dyslipidemia, and cerebral stroke).

Conclusions: As the proportion of LVSD cases increases progressively with age, it is expected to simulate a future epidemic. The differences between patients' characteristics and disease patterns in urban and rural communities may favor individually tailoring preventive strategies for HF in these areas.
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http://dx.doi.org/10.1253/circj.72.349DOI Listing
March 2008

Long-term clinical and neurologic recovery in the hand after surgery for severe cubital tunnel syndrome.

J Hand Surg Am 2004 May;29(3):373-8

Department of Orthopaedic Surgery, Niigata Chuo Hospital, Akita City, Japan.

Purpose: Functional outcomes of cubital tunnel surgery may decline as the severity of preoperative ulnar neuropathy increases. When functional recovery will be adequate, or whether tendon transfers should be required, may be unclear. We investigated the extent of functional recovery, the duration of the recovery process, and the necessity of restoring intrinsic muscle function in patients with severe cubital tunnel syndrome after surgery.

Methods: We retrospectively studied outcomes after cubital tunnel release in 15 patients with marked intrinsic muscle atrophy, claw-hand deformity, immeasurable (electrically silent) sensory and motor nerve conduction velocities, and Semmes-Weinstein test (SWT) results ranging from purple (3.84-4.31) to red (4.56-6.65). We evaluated subjective (numbness and activities of daily living [ADL] disturbances), objective (manual muscle testing [MMT] of index-finger abduction, and SWT), and neurophysiologic (nerve conduction velocity) outcomes. Overall functional outcome was evaluated by Akahori's criteria.

Results: At a median follow-up evaluation of 4.5 years all outcomes had improved. Numbness was gone in 5 patients and greatly reduced in 9 patients; 6 patients reported slight difficulties in ADLs; and 9 patients had no difficulties. Motor nerve conduction velocity was measurable (mean, 35.3 m/s) in all 15 patients and sensory nerve conduction velocity was measurable (mean, 43.4 m/s) in 12. Recoveries in nerve conduction velocities persisted beyond 2 years. The SWT results were blue (3.22-3.61) in 6 patients, purple (3.84-4.31) in 8 patients, and red (4.56-6.65) in 1 patient. MMT of index finger abduction was grade 4 or 5 in 11 of 15 patients. Half the patients over 70 years old, however, were grade 3 or less. Akahori's criteria were excellent in 3 patients, good in 6 patients, and fair in 6 patients.

Conclusions: Patients with severe intrinsic muscle atrophy and absent motor and sensory nerve conduction velocities can expect satisfactory long-term functional results after surgery. Function continues to improve beyond 2 years. Restoring index finger abduction is not always necessary for ADLs, although recovery requires several years and is poorer in the elderly.
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http://dx.doi.org/10.1016/j.jhsa.2004.01.010DOI Listing
May 2004

[The impact of resistance testing of HIV-1 to the HIV clinical setting in Japan].

Nihon Rinsho 2002 Apr;60(4):769-74

Department of Laboratory Medicine, Tokyo Medical University.

Recently, resistance testing of HIV-1 become available to clinicians in Japan. Retrospective studies show that results of these tests predict the response to salvage therapy, and randomized, controlled clinical trials show short-term virologic benefits of resistance testing as a guide to selecting salvage regimens. But the ultimate role for resistance testing in HIV clinical practice is yet to be determined fully. Both phenotypic and genotypic tests have yet to be fully standardized. Interpretation of results is still an 'art', and access to testing is still limited by cost considerations. This review will describe some of the tools that are available for interpreting genotypic assays.
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April 2002
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