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1.
Chem Sci ; 8(8): 5434-5439, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28970922

ABSTRACT

Highly efficient ammonia synthesis at a low temperature is desirable for future energy and material sources. We accomplished efficient electrocatalytic low-temperature ammonia synthesis with the highest yield ever reported. The maximum ammonia synthesis rate was 30 099 µmol gcat-1 h-1 over a 9.9 wt% Cs/5.0 wt% Ru/SrZrO3 catalyst, which is a very high rate. Proton hopping on the surface of the heterogeneous catalyst played an important role in the reaction, revealed by in situ IR measurements. Hopping protons activate N2 even at low temperatures, and they moderate the harsh reaction condition requirements. Application of an electric field to the catalyst resulted in a drastic decrease in the apparent activation energy from 121 kJ mol-1 to 37 kJ mol-1. N2 dissociative adsorption is markedly promoted by the application of the electric field, as evidenced by DFT calculations. The process described herein opens the door for small-scale, on-demand ammonia synthesis.

2.
Andrology ; 5(4): 824-831, 2017 07.
Article in English | MEDLINE | ID: mdl-28718531

ABSTRACT

Azoospermia affects up to 1% of adult men. Non-obstructive azoospermia is a multifactorial disorder whose molecular basis remains largely unknown. To date, mutations in several genes and multiple submicroscopic copy-number variations (CNVs) have been identified in patients with non-obstructive azoospermia. The aim of this study was to clarify the contribution of nucleotide substitutions in known causative genes and submicroscopic CNVs in the genome to the development of non-obstructive azoospermia. To this end, we conducted sequence analysis of 25 known disease-associated genes using next-generation sequencing and genome-wide copy-number analysis using array-based comparative genomic hybridization. We studied 40 Japanese patients with idiopathic non-obstructive azoospermia. Functional significance of molecular alterations was assessed by in silico analyses. As a result, we identified four putative pathogenic mutations, four rare polymorphisms possibly associated with disease risk, and four probable neutral variants in 10 patients. These sequence alterations included a heterozygous splice site mutation in SOHLH1 and a hemizygous missense substitution in TEX11, which have been reported as causes of non-obstructive azoospermia. Copy-number analysis detected five X chromosomal or autosomal CNVs of unknown clinical significance, in addition to one known pathogenic Y chromosomal microduplication. Five patients carried multiple molecular alterations. The results indicate that monogenic and oligogenic mutations, including those in SOHLH1 and TEX11, account for more than 10% of cases of idiopathic non-obstructive azoospermia. Furthermore, this study suggests possible contributions of substitutions in various genes as well as submicroscopic CNVs on the X chromosome and autosomes to non-obstructive azoospermia, which require further validation.


Subject(s)
Azoospermia/genetics , Comparative Genomic Hybridization , DNA Mutational Analysis/methods , Fertility/genetics , High-Throughput Nucleotide Sequencing , Multifactorial Inheritance , Mutation , Polymorphism, Genetic , Azoospermia/diagnosis , Azoospermia/physiopathology , Basic Helix-Loop-Helix Transcription Factors/genetics , Cell Cycle Proteins , Chromosomal Proteins, Non-Histone/genetics , Chromosomes, Human, X , Chromosomes, Human, Y , DNA Copy Number Variations , Gene Dosage , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Japan , Male , Phenotype , Predictive Value of Tests
3.
Reprod Domest Anim ; 52 Suppl 2: 354-358, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27859771

ABSTRACT

The intent of this contribution is to provide an update of the progress we have made towards developing a method/treatment to permanently sterilize cats. Our approach employs two complementary methodologies: RNA interference (RNAi) to silence genes involved in the central control of reproduction and a virus-based gene therapy system intended to deliver RNAi selectively to the hypothalamus (where these genes are expressed) via the systemic administration of modified viruses. We selected the hypothalamus because it contains neurons expressing Kiss1 and Tac3, two genes essential for reproduction and fertility. We chose the non-pathogenic adeno-associated virus (AAV) as a vector whose tropism could be modified to target the hypothalamus. The issues that must be overcome to utilize this vector as a delivery vehicle to induce sterility include modification of the wild-type AAV to target the hypothalamic region of the brain with a simultaneous reduction in targeting of peripheral tissues and non-hypothalamic brain regions, identification of RNAi targets that will effectively reduce the expression of Kiss1 and Tac3 without off-target effects, and determination if neutralizing antibodies to the AAV serotype of choice are present in cats. Successful resolution of these issues will pave the way for the development of a powerful tool to induce the permanent sterility in cats.


Subject(s)
Cats , Contraception/veterinary , Dependovirus , Gene Silencing , Genetic Vectors , Hypothalamus , Animals , Contraception/methods , Gene Expression/drug effects , Genetic Engineering/methods , Genetic Engineering/veterinary , Infertility/etiology , Infertility/veterinary , Kisspeptins/antagonists & inhibitors , Kisspeptins/genetics , Neurokinin B/antagonists & inhibitors , Neurokinin B/genetics , RNA Interference
4.
Eur J Obstet Gynecol Reprod Biol ; 205: 54-9, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27566223

ABSTRACT

OBJECTIVE: Although the postoperative use of hormonal treatment for endometriosis is recommended in the European Society of Human Reproduction and Embryology guidelines to prevent the recurrence of endometriosis-associated dysmenorrhoea, hormonal treatment may not be necessary for all patients who undergo surgical treatment for endometriosis. The aim of this study was to clarify the determinant factors that predict the recurrence of endometriosis after surgery in order to develop personalized hormonal treatment recommendations. Factors associated with the recurrence of endometrioma and pain were investigated independently to identify the likelihood of recurrence in each individual patient. STUDY DESIGN: Between 2008 and 2013, 352 patients underwent surgery and were diagnosed with endometriosis based on pathological findings at the study hospital. Among these patients, 191 experienced a recurrence of endometrioma in the absence of pre- or postoperative hormonal treatment. Various clinical factors such as pre-operative pain, intra-operative findings and postoperative improvement of pain were compared between patients who experienced recurrence after surgery and those who did not. RESULTS: The cumulative 5-year recurrence rate of endometrioma was 28.7% among the 191 patients who did not undergo pre- or postoperative hormonal treatment. Significant differences were detected in maximum tumour diameter, revised American Society for Reproductive Medicine score (r-ASRM score), operative time and operative blood loss between patients in the recurrent endometrioma group and the non-recurrent endometrioma group; only the r-ASRM score was significantly correlated with recurrence of endometrioma in the multivariate analysis. The cumulative 5-year rate of persistent/recurrent pain was 33.4%. There were significant differences in the postoperative improvement of pain between the persistent/recurrent pain group and the non-recurrent pain group according to the univariate and multivariate analyses. CONCLUSION: This study suggests that the risk factors for recurrence of endometrioma differ from the risk factors for recurrence of pain. The use of postoperative hormonal treatment should be considered based on the dominant risk factors and needs of each patient.


Subject(s)
Endometriosis/surgery , Laparoscopy , Ovarian Diseases/surgery , Pain/diagnosis , Adult , Age Factors , Endometriosis/diagnosis , Female , Humans , Ovarian Diseases/diagnosis , Postoperative Period , Recurrence , Risk Factors , Treatment Outcome
6.
Transpl Infect Dis ; 14(1): 49-56, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22093089

ABSTRACT

Systemic rotavirus infection, such as rotavirus antigenemia, has been found in immunocompetent rotavirus gastroenteritis patients. However, the pathogenesis of rotavirus infection in immunocompromised transplant recipients remains unclear. Enzyme-linked immunosorbent assay was used to measure rotavirus antigen levels in serially collected serum samples obtained from 62 pediatric patients receiving allogeneic hematopoietic stem cell transplants (HSCT). Rotavirus antigen was detected in 43 (6.8%) of 633 serum samples (8 of 62 patients). The duration of rotavirus antigenemia ranged between 1 and 10 weeks, and diarrhea was concurrent with rotavirus antigenemia in Cases 3, 6, 7, and 8. The level of viral antigen in the transplant recipients (0.19 ± 0.20) was significantly lower than that observed in serum samples collected from immunocompetent patients on either day 1 (0.49 ± 0.18, P = 0.0011) or day 3 (0.63 ± 0.09, P = 0.0005). A patient who received a graft from a human leukocyte antigen (HLA)-mismatched donor was at significant risk for rotavirus antigenemia (P = 0.024; odds ratio = 9.44) in comparison to patients who received grafts from HLA-matched donors. Although the duration of antigenemia was clearly longer in HSCT patients than in immunocompetent rotavirus gastroenteritis patients, the levels of viral antigen were not as high. Therefore, mismatched HLA may be a risk factor for rotavirus antigenemia after HSCT.


Subject(s)
Antigens, Viral/blood , Hematopoietic Stem Cell Transplantation/adverse effects , Rotavirus Infections/virology , Rotavirus/immunology , Viremia/immunology , Adolescent , Antibodies, Viral/blood , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , HLA Antigens/immunology , Humans , Infant , Male , Risk Factors , Rotavirus/isolation & purification , Rotavirus Infections/blood , Rotavirus Infections/physiopathology , Transplantation, Homologous/adverse effects , Viremia/virology
7.
Gene Ther ; 17(9): 1181-90, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20827278

ABSTRACT

Duchenne muscular dystrophy is a fatal, genetic disorder in which dystrophin-deficient muscle progressively degenerates, for which dystrophin gene transfer could provide effective treatment. The host immune response to dystrophin, however, is an obstacle to therapeutic gene expression. Understanding the dystrophin-induced host immune response will facilitate the discovery of strategies to prolong expression of recombinant dystrophin in dystrophic muscle. Using whole-body irradiation of the dystrophic mdx mouse before gene transfer, we temporally removed the immune system; a 600 rad dose removed peripheral immune cells, which were restored by self-reconstitution, and a 900 rad dose removed central and peripheral immune cells, which were restored by adoptive transfer of bone marrow from a syngeneic, dystrophin-normal donor. The anti-dystrophin humoral response was delayed and dystrophin expression was partially preserved in irradiated, vector-treated mice. Nonirradiated, vector-treated control mice lost muscle dystrophin expression completely, had an earlier anti-dystrophin humoral response and demonstrated muscle fibers focally surrounded with T cells. We conclude that dystrophin gene transfer induced anti-dystrophin humoral immunity and cell-mediated responses that were significantly diminished and delayed by temporal removal of the host central or peripheral immune cells. Furthermore, manipulation of central immunity altered the pattern of regulatory T cells in muscle.


Subject(s)
Dystrophin/genetics , Immunity, Humoral/radiation effects , Muscular Dystrophy, Duchenne/immunology , Whole-Body Irradiation , Animals , DNA, Complementary/administration & dosage , Dystrophin/immunology , Gene Transfer Techniques , Genetic Vectors , Mice , Mice, Inbred mdx , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/radiation effects
8.
Kyobu Geka ; 60(1): 31-4, 2007 Jan.
Article in Japanese | MEDLINE | ID: mdl-17249535

ABSTRACT

Malignant pleural mesothelioma carries a poor prognosis, for which no standard therapy has been established. We report 15 cases of malignant pleural mesothelioma experienced since 2000 focusing on their clinical features. They included 14 male and 1 female aged 38 to 81 (62.8 on average) years. All patients were diagnosed by pleural biopsy under thoracoscopic guidance. Histology of the pleural biopsy specimen showed epithelial mesothelioma in 8 patients, biphasic mesothelioma in 3, sarcomatous mesothelioma in 2 and desmoplastic malignant mesothelioma (DMM) in 2. Twelve patients received chemotherapy. Of these, 3 were followed by surgery. In addition to 2 of these 3 patients, 2 underwent extrapleural pneumonectomy (EPP) without adjuvant treatment. Remaining 1 received palliative treatment only. As a result, 6 patients are surviving, 7 died of primary diseases and 2 died of other diseases. The longest survival time with chemotherapy is 41 months in a surviving patient with epithelial mesothelioma and that with EPP is 25 months in a surviving patient with DMM. The 2-year survival rate of the 14 patients was 44.4% and the median survival time in patients with epithelial mesothelioma was 30.6 months.


Subject(s)
Mesothelioma/therapy , Pleural Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mesothelioma/mortality , Middle Aged , Pleural Neoplasms/mortality , Survival Rate
9.
Spinal Cord ; 44(6): 362-8, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16331312

ABSTRACT

STUDY DESIGN: Analysis of answers to a new questionnaire. OBJECTIVE: To examine current practice patterns of physicians in the urological surveillance and management of spinal cord injury (SCI) patients in Japan. SETTING: Nationwide questionnaire survey to physicians in Japan. METHODS: A Japanese version of the 14-item questionnaire survey carried out in US was mailed to 770 members of the Japanese Neurogenic Bladder Society (JNBS). RESULTS: We received answers to our questionnaire from 333 (43.2%) members of JNBS. The responders were all urologists. For surveillance of the upper urinary tract (UUT), 239 (71.8%) respondents preferred abdominal ultrasound. Cystometry was performed routinely by 174 (52.3%) respondents for the evaluation of vesicourethral function. Cystoscopy was carried out in cases of hematuria (88.0%) and bladder stone (55.3%). Surveillance of the urinary tract was performed every year in 154 (46.2%). For detection of bladder cancer, which 119 (37.9%) respondents have experienced, 94.9% physicians perform cystoscopy, 76.3% urinary cytology, and 60.4% ultrasound. For initial treatment of detrusor-sphincter dyssynergia (DSD), 225 (69.2%) respondents chose alpha-blocker, and 94 (28.9%) chose clean intermittent catheterization (CIC) with/without anticholinergic agent(s). For initial treatment of overactive bladder, 245 (74.7%) chose anticholinergic agent(s) only and 63 (19.2%) chose anticholinergic agent(s) with CIC. For initial treatment of areflexic bladder, 233 (73.7%) chose CIC and 63 (19.9%) chose Credé maneuver or tapping. CONCLUSIONS: This survey shows that there are some differences in urological surveillance and management of SCI patients between Japan and the US. Reasons for the discrepancy should be examined.


Subject(s)
Population Surveillance/methods , Practice Patterns, Physicians'/statistics & numerical data , Spinal Cord Injuries/diagnosis , Spinal Cord Injuries/therapy , Urologic Diseases/diagnosis , Urologic Diseases/therapy , Comorbidity , Health Care Surveys , Incidence , Japan/epidemiology , Spinal Cord Injuries/epidemiology , Surveys and Questionnaires , Urologic Diseases/epidemiology
10.
Int J Gynecol Cancer ; 15(2): 224-7, 2005.
Article in English | MEDLINE | ID: mdl-15823103

ABSTRACT

We report five cases of carboplatin (CBDCA) hypersensitivity after weekly low-dose paclitaxel (60 mg/m2)/CBDCA (area under the concentration curve = 2) therapy in patients with recurrent ovarian cancer receiving multiple platinum-based chemotherapy. Paclitaxel and CBDCA therapy was indicated as second-line chemotherapy in one patient and as third line in four patients with recurrent disease. The range of previously administered total CBDCA was 2582-9589 mg, and the CBDCA area under the concentration curve of the first treatment exhibited appropriate intensity (mean, 1.92 +/- 0.10; range, 1.76-2.10) in all patients. However, one patient exhibited severe hypersensitivity reactions including cardiac arrest and apnea, and another four patients developed eruptions, hypotension, and tachycardia soon after administration of CBDCA. Our report suggested that CBDCA hypersensitivity was correlated with the total dose of previously administered platinum agents and that CBDCA should be excluded in patients who have received multiple platinum-based chemotherapy, even in platinum-sensitive cases, because CBDCA hypersensitivity can occur even with low-dose CBDCA administration.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/adverse effects , Carboplatin/therapeutic use , Drug Hypersensitivity , Ovarian Neoplasms/drug therapy , Aged , Area Under Curve , Cisplatin/administration & dosage , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage
11.
J Comput Chem ; 25(2): 179-88, 2004 Jan 30.
Article in English | MEDLINE | ID: mdl-14648617

ABSTRACT

Time-dependent density functional theory calculations have been performed for the excited states of psoralen, 5-methoxypsoralen, and 8-methoxypsoralen in systems and furan and pyrone monoadducts bonded to a thymine residue. The theoretical assignments to ultraviolet (UV) absorption spectra of isolated systems have been performed. The present calculations have clarified that the excitation energies of the first singlet excited (S1) state of monoadducts are blue-shifted compared with the isolated systems. It is shown that, in particular, the S1 excitation energy of the pyrone monoadduct is significantly blue-shifted and, therefore, the pyrone monoadduct is not excited by UV-A light (300-400 nm), which is used in the photochemotherapy.


Subject(s)
Furocoumarins/chemistry , Thymine/chemistry , Intercalating Agents/chemistry , Kinetics , Methoxsalen/chemistry , Models, Molecular , Molecular Conformation
12.
Neurology ; 60(11): 1799-804, 2003 Jun 10.
Article in English | MEDLINE | ID: mdl-12796534

ABSTRACT

OBJECTIVE: To study dysferlin gene mutations and genotype-phenotype correlations in Japanese patients with Miyoshi myopathy (MM). BACKGROUND: MM is an autosomal recessive distal muscular dystrophy that arises from mutations in the dysferlin gene. This gene is also mutated in families with limb girdle muscular dystrophy 2B. METHODS: The authors examined 25 Japanese patients with MM. Genomic DNA was extracted from the peripheral lymphocytes of the patients. The PCR products of each of 55 exons were screened by single strand conformation polymorphism or direct sequencing from the PCR fragments. RESULTS: The authors identified 16 different mutations in 20 patients with MM; 10 were novel. Mutations in Japanese patients are distributed along the entire length of the gene. CONCLUSIONS: Four mutations (C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent in this population, accounting for 60% of the mutations in this study. This study revealed that the G3370T mutation was associated with milder forms of MM and the G3510A mutation was associated with a more severe form.


Subject(s)
Membrane Proteins , Muscle Proteins/genetics , Muscular Dystrophies/diagnosis , Muscular Dystrophies/genetics , Mutation , Adult , Creatine Kinase/blood , DNA Mutational Analysis , Dysferlin , Female , Genotype , Humans , Japan/epidemiology , Male , Middle Aged , Muscular Dystrophies/epidemiology , Phenotype , Polymorphism, Genetic
13.
Int J Gynecol Cancer ; 12(3): 304-7, 2002.
Article in English | MEDLINE | ID: mdl-12060453

ABSTRACT

We report the effect of low-dose mitomycin C, etoposide, and cisplatin (low-dose MEP) therapy for three patients with invasive vulvar Paget's disease (invasive VPD) who declined radical vulvectomy and skin grafting. One patient achieved a complete response, while the other two showed partial responses (PR) without grade 3 or 4 adverse effects. The two patients with PR were undergone partial vulvectomy and inguinal lymph node dissection. All patients have no sign of recurrence for 10 months after chemotherapy. Our present results suggest that low-dose MEP is an effective and safe chemotherapy for invasive VPD and low-dose MEP may significantly improve postoperative quality of life in patients with invasive VPD by avoiding extensive vulvar resection and skin grafting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Paget Disease, Extramammary/drug therapy , Vulvar Neoplasms/drug therapy , Aged , Cisplatin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Mitomycin/administration & dosage , Neoplasm Invasiveness/pathology , Neoplasm Staging , Paget Disease, Extramammary/pathology , Quality of Life , Vulvar Neoplasms/pathology
14.
J Mol Biol ; 312(5): 935-47, 2001 Oct 05.
Article in English | MEDLINE | ID: mdl-11580240

ABSTRACT

Escherichia coli PriA is a primosome assembly protein with 3' to 5' helicase activity whose apparent function is to promote resumption of DNA synthesis following replication-fork arrest. Here, we describe how initiation of helicase activity on DNA forks is influenced by both fork structure and by single-strand DNA-binding protein. PriA could recognize and unwind forked substrates where one or both arms were primarily duplex, and PriA required a small (two bases or larger) single-stranded gap at the fork in order to initiate unwinding. The helicase was most active on substrates with a duplex lagging-strand arm and a single-stranded leading-strand arm. On this substrate, PriA was capable of translocating on either the leading or lagging strands to unwind the duplex ahead of the fork or the lagging-strand duplex, respectively. Fork-specific binding apparently orients the helicase domain to unwind the lagging-strand duplex. Binding of single-strand-binding protein to forked templates could inhibit unwinding of the duplex ahead of the fork but not unwinding of the lagging-strand duplex or translocation on the lagging-strand template. While single-strand-binding protein could inhibit binding of PriA to the minimal, unforked DNA substrates, it could not inhibit PriA binding to forked substrates. In the cell, single-strand-binding protein and fork structure may direct PriA helicase to translocate along the lagging-strand template of forked structures such that the primosome is specifically assembled on that DNA strand.


Subject(s)
DNA Helicases/metabolism , DNA Replication , DNA, Single-Stranded/metabolism , DNA-Binding Proteins/metabolism , Escherichia coli/enzymology , Base Sequence , DNA Primers , DNA, Single-Stranded/chemistry , DNA, Single-Stranded/genetics , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Escherichia coli/genetics , Models, Biological , Molecular Sequence Data , Nucleic Acid Conformation , Protein Binding , Replication Protein A , Substrate Specificity , Templates, Genetic
15.
Transplantation ; 72(6): 1037-42, 2001 Sep 27.
Article in English | MEDLINE | ID: mdl-11579297

ABSTRACT

BACKGROUND: Due to a severe shortage of suitable cadaveric allografts for children awaiting kidney transplants, we have performed a series of ABO-incompatible living kidney transplantations (LKT) at our institution. METHODS: Between July 1989 and March 2000, 16 pediatric patients (3 female, 13 male) underwent ABO-incompatible LKT. The mean age at transplantation was 10.9+/-4.3 years (range 5.1-15.0 years). The donor to recipient ABO blood antigen incompatibility was as follows: A1-->O, 5 patients; B-->O, 6 patients; A1B-->B, 2 patients; and A1B -->B, A1-->B, or B-->A1, 1 patient each. The median pretransplantation anti-A1 titers of eight A-incompatible recipients were 1:128 (IgM, range 1:16 to 1:512) and 1:32 (IgG, range 1:2 to 1:128). Median anti-B titers of seven B-incompatible recipients were 1:32 (IgM, range 1:4 to 1:128) and 1:8 (IgG, range 1:2 to 1:64). All patients received three or four sessions of plasmapheresis (PP) and/or immunoadsorption (IA) to remove the anti-A and/or anti-B antibodies before transplantation. Immunosuppression initially consisted of cyclosporine, methylprednisolone, cyclophosphamide, and antilymphocyte globulin. Splenectomy was performed on all recipients at the time of transplantation. RESULTS: The patients were followed for 6 to 122 months with a mean follow-up of 63 months. All 16 recipients who underwent ABO-incompatible LKT achieved a pretransplant isoagglutinin titer less than 1:8 with 3-4 sessions of PP/IA treatment. Of 16 patients, 10 patients had rebound increase in their IgM and/or IgG anti-A/B titers to greater than 1:64 or predepletion levels within 10 days posttransplantation. In addition, nine patients developed renal dysfunction in association with the rebound increase in their anti-A/B. One patient lost his graft because of uncontrolled delayed hyperacute rejection, whereas eight other recipients recovered completely with pulse steroids and PP/IA therapy. After the third week posttransplant, there was no correlation between the occurrence of AR and their isoagglutinin titers. Moreover, no antibody-mediated rejection was observed, even in recipients with continued high titer anti-A and/or anti-B antibodies. Patient survival is 100% to date. The actuarial 1-year and 5-year graft survival rates are 87% and 85%, respectively. No fatal infectious complications occurred despite the combination of splenectomy and immunosuppressive drugs. CONCLUSIONS: We have demonstrated that with adequate pre- and posttransplant management, successful kidney transplantation across the ABO barrier is possible in the pediatric population. "Accommodation" of the allografts occurred within 2 weeks of transplantation. Subsequently, the long-term graft outcome of ABO-incompatible LKT was comparable to that of ABO-compatible LKT.


Subject(s)
ABO Blood-Group System , Blood Group Incompatibility , Kidney Transplantation , Living Donors , Adolescent , Child , Female , Humans , Immunosorbent Techniques , Immunosuppressive Agents/therapeutic use , Male , Plasmapheresis , Splenectomy , Time Factors , Transplantation, Homologous , Treatment Outcome
16.
Gene ; 274(1-2): 93-9, 2001 Aug 22.
Article in English | MEDLINE | ID: mdl-11675001

ABSTRACT

The 23-kDa proteolipid subunit of mouse vacuolar-type proton-translocating ATPase (V-ATPase) was predicted to be a hydrophobic polypeptide of 205 amino acid residues with five putative transmembrane segments. It exhibits sequence similarity to Vma16p of Saccharomyces cerevisiae and vha-4 of Caenorhabdittis elegans (83 and 84%, respectively). Southern blot analysis indicated that the proteolipid is encoded by a single gene, Atp6f, in the mouse genome. Atp6f was mapped to approximately 55 cM on chromosome 4, and its genomic organization is similar to that of the human gene: 8 exons separated by 7 introns, with boundaries matching the GT-AG rule. RNA blotting demonstrated that Atp6f is transcribed as 1.0- and 1.8-kb mRNAs in multiple tissues to varying degrees. The major transcription initiation sites are at -13 and -58 bp upstream of the translation initiation codon. The epitope-tagged 23-kDa protoelipid was localized in endomembrane organelles in CHO cells, as expected for a component of a vacuolar-type proton pump.


Subject(s)
Vacuolar Proton-Translocating ATPases/genetics , Alternative Splicing , Amino Acid Sequence , Animals , Base Sequence , CHO Cells , Chromosome Mapping , Cloning, Molecular , Cricetinae , DNA/chemistry , DNA/genetics , DNA, Complementary/chemistry , DNA, Complementary/genetics , Exons , Gene Expression , Genes/genetics , Introns , Male , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Molecular Sequence Data , Protein Subunits , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Tissue Distribution , Transcription Initiation Site , Vacuolar Proton-Translocating ATPases/metabolism
17.
J Physiol Pharmacol ; 52(3): 391-406, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11596858

ABSTRACT

The present study examined the expression of 73-kDa of heat shock cognate protein (HSC70), 72-kDa of heat shock protein (HSP70) and 47-kDa of HSP (HSP47) observed in the ulcer healing process in rats. Gastric ulcers were induced by a luminal application of acetic acid in male Donryu rats. During the ulcer healing process, the expression of HSPs in the ulcerated tissue was determined. A high level of HSC70 expression was observed both in the normal mucosa and ulcerated tissue, but the level did not change upon ulceration and ulcer healing. While HSP70 and HSP47 were markedly expressed in the ulcer base during ulceration, and decreased with ulcer healing. HSP70 expression in the ulcer margin was gradually increased with ulcer healing. Omeprazole accelerated the healing of gastric ulcers with strong inhibition of gastric acid secretion, while indomethactin delayed in ulcer healing despite slight inhibition of gastric acid secretion. Omperazole enhanced the expression of HSP70 both in the ulcer margin and base, but it reduced HSP47 expression in the ulcer base Indomethacin markedly enhanced HSP47 expression only in the ulcer base. In conclusion, the expression of HSP70 and HSP47 is changed during ulcer healing. Furthermore, it was suggested that the enhanced expression of HSP70 is involved in acceleration of ulcer healing, but overexpression of HSP47 is involved in delayed ulcer healing.


Subject(s)
HSP70 Heat-Shock Proteins/physiology , Heat-Shock Proteins/physiology , Stomach Ulcer/physiopathology , Animals , HSC70 Heat-Shock Proteins , HSP47 Heat-Shock Proteins , Indomethacin/pharmacology , Male , Omeprazole/pharmacology , Rats , Stomach Ulcer/drug therapy
18.
J Mol Biol ; 312(2): 311-22, 2001 Sep 14.
Article in English | MEDLINE | ID: mdl-11554788

ABSTRACT

The repressor of bacteriophage Mu functions in the establishment and maintenance of lysogeny by binding to Mu operator DNA to shut down transposition. A domain at its N terminus functions in DNA binding, and temperature-sensitive mutations in this domain can be suppressed by truncations at the C terminus. To understand the role of the C-terminal tail in DNA binding, a fluorescent probe was attached to the C terminus to examine its environment and its movement with respect to the DNA binding domain. The emission spectrum of this probe indicated that the C terminus was in a relatively hydrophobic environment, comparable to the environment of the probe attached within the DNA-binding domain. Fluorescence of two tryptophan residues located within the DNA-binding domain was quenched by the probe attached to the C terminus, indicating that the C terminus is in close proximity to this domain. Addition of DNA, even when it did not contain operator DNA, reduced quenching of tryptophan fluorescence, indicating that the tail moves away from the DNA-binding domain as it interacts with DNA. The presence of the tail also produced a trypsin hypersensitive site within the DNA-binding domain; mutant repressors with an altered or truncated C terminus were relatively resistant to cleavage at this site. Interaction of the wild-type repressor with DNA greatly reduced cleavage at the site. A repressor with a temperature-sensitive mutation in the DNA-binding domain was especially sensitive to cleavage by trypsin even in the presence of DNA, and the C-terminal tail failed to move in the presence of DNA at elevated temperatures. These results indicate that the tail sterically inhibits DNA binding and that it moves during establishment of repression. Such conformational changes are likely to be involved in communication between repressor protomers for cooperative DNA binding.


Subject(s)
Bacteriophage mu , DNA/metabolism , Repressor Proteins/chemistry , Repressor Proteins/metabolism , Amino Acid Sequence , Bacteriophage mu/genetics , DNA/genetics , Energy Transfer , Fluorescence , Kinetics , Molecular Sequence Data , Operator Regions, Genetic/genetics , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Protein Binding , Protein Structure, Tertiary , Sequence Analysis, Protein , Temperature , Trypsin/metabolism
19.
Nihon Hinyokika Gakkai Zasshi ; 92(5): 560-5, 2001 Jul.
Article in Japanese | MEDLINE | ID: mdl-11517566

ABSTRACT

PURPOSE: To increase the management of self-catheterization in children of school age, a catheter kit consisting of hydrophilic catheter and a packet containing sterilized water was developed. We evaluated the lubricating characteristic and clinical efficacy of this new catheter kit. MATERIALS AND METHODS: The catheter kit used in the study was a pocket-size plastic container in which a polyurethane catheter coated with hydrophilic polymer and a packet containing sterilized water were packed in combination. The lubricating characteristic of catheter was assessed by the measurement of friction value. For clinical assessment, male children aged over 6 years old who were doing self-catheterization at 17 medical institutions nationwide were selected as the subjects. The 32 children who had given informed consent (mean age: 11.6 years old) were asked to use the catheter kit continuously for 1 week. The results were investigated by a questionnaire survey in which the assessment before and after the use was expressed in scores. At the same time, urinalysis and urine culture were examined. RESULTS: The friction value of hydrophilic catheter was equivalent to or less than that observed by applying a lubricant to the conventional catheter. The comparison of conventional catheter with the kit indicated significantly higher scores (assessment in 5 grades expressed in scores) for the portability and operability of the kit. Though there was no significant difference in the ease of insertion between the two catheters, there were several comments that the kit got stuck in the urethra when it was withdrawn. The global assessment gave a significantly higher score to the kit and 30 (94%) of the 32 children wanted to use the kit continuously. No increase in hematuria which caused a clinical problem or no new apparent urinary tract infection occurred after the use of the kit. CONCLUSIONS: Compared with the conventional catheter, the hydrophilic catheter kit highly satisfied a large number of children at the time of self-catheterization. Depending on the condition of children, the kit is considered useful for continued self-catheterization for a long term.


Subject(s)
Self Care , Urinary Catheterization/standards , Child , Disposable Equipment/standards , Humans , Male , Urinary Catheterization/instrumentation , Urologic Diseases/therapy
20.
No Shinkei Geka ; 29(5): 439-44, 2001 May.
Article in Japanese | MEDLINE | ID: mdl-11449716

ABSTRACT

We present a case of tumoral multiple sclerosis in a 66-year-old male and emphasize two clinical features: (1) Multiple well-demarcated massive enhanced lesions except for the central area, which was accompanied with severe perifocal edema, occurred within the cerebral hemispheres and should be strongly considered in the diagnosis of mass lesions. The patient underwent partial removal of the mass lesion. The initial histopathological diagnosis of the surgical specimen was astrocytoma grade II. (2) Multiple lesions disappeared completely for one and half months after starting medication using steroid. The reexamination of the surgical specimen was compatible with that of multiple sclerosis. Again, half a month after remission, multiple enhanced lesions without perifocal edema developed in the cerebral and cerebellar hemisphere. The difficulty of the initial diagnosis of multiple sclerosis with severe perifocal edema was discussed, based on our experience.


Subject(s)
Brain Edema/pathology , Multiple Sclerosis/diagnosis , Aged , Astrocytoma/complications , Astrocytoma/pathology , Astrocytoma/surgery , Brain Edema/complications , Brain Edema/surgery , Brain Neoplasms/complications , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Humans , Magnetic Resonance Imaging , Male , Multiple Sclerosis/complications , Multiple Sclerosis/pathology , Multiple Sclerosis/surgery
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