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Biomedical subjects

Ryuichi Kato

Publications and source records attributed to Ryuichi Kato.

At least 37 records · Page 2Linked to original sources
PubMed2005

Noxa is a critical mediator of p53-dependent motor neuron death after nerve injury in adult mouse.

Axotomy-induced motor neuron death occurs within a week in the neonatal rat and mouse. However, slowly progressive motor neuron death, which takes more than a month, occurs after axotomy in the adult mouse (C57BL/6) but not in the adult rat (Wistar). Here we demonstrate that expression of a p53-inducible Bcl-2 homology domain 3 (BH3)-only protein, Noxa, is enhanced in axotomized neurons of the adult mouse but not in the adult rat. In p53-deficient mice, slowly progressive neuronal death was suppressed and accompanied by reduced Noxa expression after axotomy. However, a minor response of Noxa expression was still observed after axotomy in p53-deficient mice, suggesting that p53-independent Noxa expression occurs to a minor extent. Noxa-deficient mice were used to confirm the consequence of Noxa expression in nerve-injured mouse motor neurons. In Noxa-deficient mice, axotomy-induced motor neuron death was suppressed. Furthermore, among the BH3-only protein members examined, Noxa exhibited the most marked upregulation after axotomy in the mouse. In conclusion, motor neuron death seen in the adult mouse is mainly p53 dependent, and Noxa is a major executor for axotomy-induced motor neuron death in the adult mouse, as a mediator located downstream of p53.

Animals↗
PubMed2005

Levels of matrix metalloproteinase-1 in patients with and without coronary artery disease and relation to complex and noncomplex coronary plaques.

We investigated the association between serum levels of matrix metalloproteinase-1 (MMP-1) and coronary artery disease (CAD) in 185 patients who underwent elective coronary angiography. MMP-1 levels did not differ between patients who had CAD and those who did not and did not correlate with the number of >50% stenotic vessels or segments, but MMP-1 levels were significantly higher in patients who had CAD and complex coronary lesions than in those who did not have such lesions and those who did not have CAD. High serum levels of MMP-1 were associated with the presence of complex lesions in patients who had CAD.

Aged↗
PubMed2005

Prevalence of female sexual dysfunction symptoms and its relationship to quality of life: a Japanese female cohort study.

OBJECTIVES: To clarify the age prevalence of female sexual dysfunction and the factors that contribute to the varying frequency of sexual intercourse and satisfaction with sexual life in Japanese women. METHODS: Of 8956 participants (median age 57 years, range 17 to 88) in a Japanese female cohort study, 5042 (56.3%) responded. We evaluated 2095 women aged 30 to 69 years (median 48) who completed a questionnaire that queried about their sexual life. RESULTS: When women in their 30s were compared with those in their 60s, we found that the prevalence of the symptom of orgasmic disorder, sexual desire disorder, arousal disorder, and lubrication disorder had increased significantly from 15.2% to 32.2%, 27.7% to 57.9%, 29.7% to 57.9%, and 12.5% to 51.2%, respectively. Multivariate analysis showed that the rigidity of the partner's erection, orgasm, and arousal contributed significantly to sexual frequency and foreplay and orgasm to satisfaction with sexual life. CONCLUSIONS: The prevalence of female sexual dysfunction increased with age. The results of multivariate analysis indicated that favorable sexual function is important to maintain the opportunity for sexual intercourse in both men and women and that foreplay and orgasm are essential for satisfactory sexual life in women.

Adult↗
PubMed2005

Cerebral thrombotic complications in adolescent leukemia/lymphoma patients treated with L-asparaginase-containing chemotherapy.

We described the cerebral thrombotic complications developed in 2 adolescent patients treated with L-asparaginase-containing regimens. For determining risk factors, we retrospectively analysed hemostatic markers in 19 pediatric patients with leukemia or lymphoma who were treated with either 1 of the 2 L-asparaginase-containing regimens; 11 were treated with VLP1 and the remaining 8 were treated with the VLAD protocol. The data indicated that low coagulation factors in association with increased plasma D-dimer levels during or post-L-asparaginase administration combined with fresh frozen plasma infusion might have activated coagulation processes in these patients. Careful management is required to prevent such episodes in patients with markedly decreased coagulation factors and increased D-dimer levels following L-asparaginase administration.

Adolescent↗
PubMed2005

Cavernous nerve reconstruction with a biodegradable conduit graft and collagen sponge in the rat.

PURPOSE: We investigated the efficacy of a biodegradable conduit graft for axonal regeneration of the injured cavernous nerve in a rat model. MATERIALS AND METHODS: Bilateral cavernous nerves were resected in 8-week-old Sprague-Dawley rats. We interposed a nerve gap with a 4 mm poly L-lactic acid and E-caprolactone copolymer conduit. The 56 rats were divided into 4 groups, namely group 1-biodegradable conduit alone, group 2-biodegradable conduit plus collagen sponge, group 3-sham operation as a positive control and group 4-unconnected conduit as a negative control. RESULTS: Immunohistochemical study revealed that neuronal nitric oxide synthase positive nerve fibers significantly increased in all rats in the conduit graft groups at 3 months. In a retrograde tracing study with FluoroGold (Fluorochrome, Englewood, Colorado) at 3 months the conduit plus collagen group showed a significant increase in FluoroGold positive cells in major pelvic ganglia. Intracavernous pressure elicited by medial preoptic area stimulation significantly increased in all rats in the conduit graft groups, especially in the conduit plus collagen group. CONCLUSIONS: This study suggests that a biodegradable conduit is effective for axonal regeneration of the injured cavernous nerve. Moreover, a conduit with a collagen sponge facilitates axonal sprouting and re-projection to its target organ, and ensures functional recovery.

Absorbable Implants↗
PubMed2005

Molecular mechanism of ubiquitin recognition by GGA3 GAT domain.

GGA (Golgi-localizing, gamma-adaptin ear domain homology, ARF-binding) proteins, which constitute a family of clathrin coat adaptor proteins, have recently been shown to be involved in the ubiquitin-dependent sorting of receptors, through the interaction between the C-terminal three-helix-bundle of the GAT (GGA and Tom1) domain (C-GAT) and ubiquitin. We report here the crystal structure of human GGA3 C-GAT in complex with ubiquitin. A hydrophobic patch on C-GAT helices alpha1 and alpha2 forms a binding site for the hydrophobic Ile44 surface of ubiquitin. Two distinct orientations of ubiquitin Arg42 determine the shape and the charge distribution of ubiquitin Ile44 surface, leading to two different binding modes. Biochemical and NMR data strongly suggest another hydrophobic binding site on C-GAT helices alpha2 and alpha3, opposite to the first binding site, also binds ubiquitin although weakly. The double-sided ubiquitin binding provides the GAT domain with higher efficiency in recognizing ubiquitinated receptors for lysosomal receptor degradation.

ADP-Ribosylation Factors↗
PubMed2005

Erectile dysfunction following nerve-sparing radical retropubic prostatectomy and its treatment with sildenafil.

BACKGROUND: We retrospectively evaluated the erectile function after nerve-sparing radical retropubic prostatectomy (RRP) and the efficacy of sildenafil for erectile dysfunction (ED) following RRP according to the preoperative erectile function. METHODS: We evaluated 48 Japanese patients who underwent nerve-sparing RRP at the Sapporo Medical University School of Medicine, Sapporo, Japan, between January 1996 and December 2001. Erectile function following nerve-sparing RRP was assessed by a simple mailed questionnaire that was constructed for the study. RESULTS: Of the 48 patients, 36 had normal erectile function preoperatively, but for 12, function was not sufficient to penetrate. The overall estimated recovery rates of any degree of erection were 50.6% at 36 months and 94.3% at 60 months. However, that of erection sufficient to penetrate was only 17.7% at 36 months and was only seen in bilateral nerve-sparing patients. Sildenafil was effective in 9 of 13 ED patients (69.2%) in both nerve-sparing groups. When patients were divided according to preoperative erectile function, no difference was found in the efficacy rate between patients with normal function and those with ED. CONCLUSIONS: Even bilateral nerve-sparing RRP can not always guarantee a sufficient erection. However, sildenafil is effective for ED following nerve-sparing RRP regardless of the nerve-sparing procedure or preoperative erectile function. Thus, preoperative function alone, although depending on its severity, may not necessarily be a reason for exclusion from receiving nerve-sparing RRP if patients want to have the operation.

Aged↗
PubMed2005

Plasma matrix metalloproteinase-8 concentrations are associated with the presence and severity of coronary artery disease.

BACKGROUND: Interstitial collagen, especially type I, is a major component of atherosclerotic plaques and the matrix metalloproteinases (MMP) 1, 8 and 13 can initiate collagen breakdown. MMP-8 degrades type I collagen preferentially and more potently than MMP-1 or MMP-13. Although MMP-8 was thought to be produced only by neutrophils, it was recently reported to also be produced by endothelial cells, smooth muscle cells and macrophages in plaques. METHODS AND RESULTS: Plasma MMP-8 concentrations were measured in 250 patients undergoing coronary angiography for coronary artery disease (CAD: >50% stenosis), which was found in 181 patients, of whom 69 had 1-vessel, 66 had 2-vessel, and 46 had 3-vessel disease. Compared with 69 patients without CAD, the 181 with CAD had higher MMP-8 concentrations (3.5 vs 3.0 ng/ml, p < 0.001). There was a stepwise increase in MMP-8 concentration depending on the number of stenotic vessels: 3.2 in 1-vessel, 3.6 in 2-vessel, and 4.3 ng/ml in 3-vessel disease (p < 0.001). Multivariate analysis showed that MMP-8 concentration was independently associated with CAD. The odds ratio for CAD was 1.22 (95%confidence interval = 1.07-1.39) for a 1 ng/ml increase in MMP-8 concentration. CONCLUSIONS: Plasma MMP-8 concentration is associated with the presence and severity of CAD.

Aged↗
PubMed2005

Polymorphism of the 3'-untranslated region of interleukin-12 p40 gene is not associated with the presence or severity of coronary artery disease.

BACKGROUND: Interleukin (IL)-12 is thought to play an important role in the development of atherosclerosis and recently, polymorphism of the 3'-untranslated region of the IL-12 p40 gene (A1188C) was reported to be associated with diabetes and multiple sclerosis. However, the association between this genetic polymorphism and coronary artery disease (CAD) has not been studied. METHODS AND RESULTS: The frequency of this polymorphism was investigated in 555 patients undergoing coronary angiography: 395 had CAD, of whom 161 also had a myocardial infarction (MI). With regard to the IL-12 p40 polymorphism, 125 had the A/A, 268 had the A/C, and 162 had the C/C genotype. The prevalence of CAD did not differ among the groups (71%, 73%, and 69%, respectively; p= NS). The prevalence of MI was also similar among the groups (28%, 27%, and 33%, respectively; p= NS). Moreover, the number of >50% stenotic vessels, >50% stenotic segments, and < or =50% stenotic segments did not differ among the 3 groups. CONCLUSIONS: Polymorphism of IL-12 p40 gene was not found to be associated with the presence or severity of CAD, suggesting that it does not play an important role in the development of this disease.

Aged↗
PubMed2004

Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamic nature of substrate recognition.

Gangliosides play key roles in cell differentiation, cell-cell interactions, and transmembrane signaling. Sialidases hydrolyze sialic acids to produce asialo compounds, which is the first step of degradation processes of glycoproteins and gangliosides. Sialidase involvement has been implicated in some lysosomal storage disorders such as sialidosis and galactosialidosis. Neu2 is a recently identified human cytosolic sialidase. Here we report the first high resolution x-ray structures of mammalian sialidase, human Neu2, in its apo form and in complex with an inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA). The structure shows the canonical six-blade beta-propeller observed in viral and bacterial sialidases with its active site in a shallow crevice. In the complex structure, the inhibitor lies in the catalytic crevice surrounded by ten amino acids. In particular, the arginine triad, conserved among sialidases, aids in the proper positioning of the carboxylate group of DANA within the active site region. The tyrosine residue, Tyr(334), conserved among mammalian and bacterial sialidases as well as in viral neuraminidases, facilitates the enzymatic reaction by stabilizing a putative carbonium ion in the transition state. The loops containing Glu(111) and the catalytic aspartate Asp(46) are disordered in the apo form but upon binding of DANA become ordered to adopt two short alpha-helices to cover the inhibitor, illustrating the dynamic nature of substrate recognition. The N-acetyl and glycerol moieties of DANA are recognized by Neu2 residues not shared by bacterial sialidases and viral neuraminidases, which can be regarded as a key structural difference for potential drug design against bacteria, influenza, and other viruses.

Animals↗
PubMed2004

Structural basis for acceptor substrate recognition of a human glucuronyltransferase, GlcAT-P, an enzyme critical in the biosynthesis of the carbohydrate epitope HNK-1.

The HNK-1 carbohydrate epitope is found on many neural cell adhesion molecules. Its structure is characterized by a terminal sulfated glucuronyl acid. The glucuronyltransferases, GlcAT-P and GlcAT-S, are involved in the biosynthesis of the HNK-1 epitope, GlcAT-P as the major enzyme. We overexpressed and purified the recombinant human GlcAT-P from Escherichia coli. Analysis of its enzymatic activity showed that it catalyzed the transfer reaction for N-acetyllactosamine (Galbeta1-4GlcNAc) but not lacto-N-biose (Galbeta1-3GlcNAc) as an acceptor substrate. Subsequently, we determined the first x-ray crystal structures of human GlcAT-P, in the absence and presence of a donor substrate product UDP, catalytic Mn(2+), and an acceptor substrate analogue N-acetyllactosamine (Galbeta1-4GlcNAc) or an asparagine-linked biantennary nonasaccharide. The asymmetric unit contains two independent molecules. Each molecule is an alpha/beta protein with two regions that constitute the donor and acceptor substrate binding sites. The UDP moiety of donor nucleotide sugar is recognized by conserved amino acid residues including a DXD motif (Asp(195)-Asp(196)-Asp(197)). Other conserved amino acid residues interact with the terminal galactose moiety of the acceptor substrate. In addition, Val(320) and Asn(321), which are located on the C-terminal long loop from a neighboring molecule, and Phe(245) contribute to the interaction with GlcNAc moiety. These three residues play a key role in establishing the acceptor substrate specificity.

Amino Acid Motifs↗
PubMed2004

Idiopathic stuttering priapism: recovery of detumescence mechanism with temporal use of antiandrogen.

We report a case of idiopathic stuttering priapism in a 56-year-old Japanese man. We treated his recurrent priapism in stepwise fashion by withdrawal of the alpha/beta-blocker he used for hypertension, administration of low doses of an antiandrogen and baclofen, and finally by increasing the dose of antiandrogen, which lowered his testosterone to the castration level and was effective in preventing priapism. After 6 months of antiandrogen treatment, his erectile function gradually recovered to the baseline level, and he had no recurrence of priapism during the following 6 months without any medication.

Baclofen↗
PubMed2004

Erectile function following external beam radiotherapy for clinically organ-confined or locally advanced prostate cancer.

BACKGROUND: External beam radiotherapy (XRT) has been a standard treatment for clinically localized prostate cancer. However, preservation of erectile function following XRT is controversial. In this study, the influence of XRT on erectile function of patients with clinically organ-confined or locally advanced prostate cancer was retrospectively evaluated. METHODS: The study included 34 of 84 patients with organ-confined or locally advanced prostate cancer who underwent XRT between 1995 and 2002. Erectile function following radiotherapy was assessed by a simple mailed questionnaire that was constructed for the study. To determine the predictive factors for erectile dysfunction following radiotherapy, data were analyzed by multivariate analysis with the Cox proportional hazards model. RESULTS: The modality of XRT was the only factor to independently predict erectile dysfunction following XRT. The maintenance rates of erectile function were 47.6% at 1 year and 19% at 3 years in patients who received the 3-dimensional conformal radiotherapy, which were significantly higher than in those who received conventional radiotherapy (P = 0.026). CONCLUSIONS: XRT significantly reduced the maintenance rate of erectile function during the follow-up period, with the rate being 19% at 3 years in patients who received 3-dimensional conformal radiation. The XRT modality was involved in the reduction of erectile function. These results suggest that erectile dysfunction is a possible adverse event following XRT.

Aged↗
PubMed2004

Early and late complications of radical retropubic prostatectomy: experience in a single institution.

BACKGROUND: Radical retropubic prostatectomy is one of the first-line treatments for clinically organ-confined prostatic cancer. However, some studies have reported the morbidity of this procedure. We retrospectively assessed the incidence of complications of radical retropubic prostatectomy in our institution. METHODS: We reviewed 123 consecutive medical charts of prostate cancer patients who underwent radical retropubic prostatectomy between 1988 and 2001 at our institution. We evaluated intraoperative complications, early complications within 1 month postoperatively, and late complications, including anastomotic stricture and urinary incontinence. RESULTS: The median age of patients was 66 years (range, 53 to 74 years) and median follow-up duration was 44.0 months (range, 2 to 157 months). None of the patients died due to surgery-related causes. Intraoperative complications included rectal injuries in six patients (4.9%) and ureteral injury in one patient (0.8%). As for late complications, anastomotic strictures were observed in 16 patients (13.8%), and stress urinary incontinence that persisted for more than 12 months was observed in 13 patients. The estimated continence recovery rate at 12 months was 87.3%. Multivariate analysis did not reveal any predictive factor for anastomotic stricture. However, the blood loss volume and period of surgery were significant predictive factors of continence recovery. CONCLUSIONS: Radical retropubic prostatectomy was safely performed, though there were various intra- or postoperative complications that were adequately managed. Early recovery of continence was related to the blood loss volume and the surgery period. Adequate surgical experience and a meticulous technique to avoid excessive bleeding are important factors for an early recovery.

Aged↗
PubMed2004

Successful treatment of congenital systemic juvenile xanthogranuloma with Langerhans cell histiocytosis-based chemotherapy.

Juvenile xanthogranuloma (JXG), one of the most common forms of non-Langerhans cell histiocytosis (LCH), usually presents in young children as spontaneously regressing cutaneous lesions. However, the systemic type of JXG is difficult to treat in newborn infants, and fatal cases have been reported. In the patient described here, solid masses were discovered by fetal sonography during the 38th gestational week. At birth she had multiple tumors on the back, cheek, and hip as well as marked hepatosplenomegaly accompanied by respiratory failure. Laboratory results indicated pancytopenia, obstructive liver dysfunction, and coagulopathy. Brain magnetic resonance imaging revealed a tumor at the left pontine angle, and dysmorphic histiocytes were present in her spinal fluid. She was diagnosed with systemic JXG by histopathologic findings of the hip mass. The LCH-based multiagent chemotherapy including cytarabine, vincristine, methotrexate, and prednisolone ameliorated the symptoms rapidly. She was treated for 12 months and is currently doing well as a normally developing 2-year-old.

Antineoplastic Combined Chemotherapy Protocols↗