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Biomedical subjects

H Sudo

Publications and source records attributed to H Sudo.

At least 19 recordsLinked to original sources

Secondary medulla oblongata involvement following middle cervical spinal cord injury associated with latent traumatic instability in a patient with ossification of the posterior longitudinal ligament.

STUDY DESIGN: A case report. OBJECTIVES: To report a rare case of extension of edema and hemorrhage from initial C4-5 spinal injury to the medulla oblongata. SETTING: Center for Spinal Disorders and Injuries, Bibai Rosai Hospital, Japan. METHODS: A 68-year-old man with ossification of the posterior longitudinal ligament (OPLL) had sustained tetraplegia after tumbling over a stone. Initially, the patient was diagnosed with an acute C4-5 spinal cord injury without radiological abnormalities and was treated conservatively. At 7 h after the injury, the patient had an ascending neurological deficit, which required respiratory assistance. Magnetic resonance imaging revealed a marked swelling of the spinal cord above C4-5 extending to the medulla oblongata. RESULTS: Retrospective radiological assessment revealed that the spine was unstable at the injury level because of discontinuities in both anterior and posterior longitudinal ligaments. There was also signal intensity change within the retropharyngeal space at the C4-5 intervertebral disc. This injured segment was highly vulnerable to post-injury dynamic stenosis and easily sustained secondary neural damage. CONCLUSIONS: This case report emphasizes a careful radiological assessment of latent structural instability in patients with OPLL in order to detect and prevent deteriorative change in the spinal cord.

Aged↗

Burkholderia pickettii spondylitis.

STUDY DESIGN: Case report describing Burkholderia pickettii spondylitis in a healthy adult. OBJECTIVES: To describe this very rare form of spondylitis and to discuss some of the difficulties in the diagnosis of B. pickettii spondylitis. SETTING: Department of Orthopaedic Surgery, Nayoro City General Hospital, Japan. METHODS: A 48-year-old woman presented with a complaint of severe back pain radiating from the right side of her chest. Plain radiographs of the spine showed osteolytic destruction of the right side of the T10 vertebral body at T10 level, with an involvement of the pedicle. Magnetic resonance image of the spine showed a low signal intensity from the T10 vertebral body on a Tl-weighted image and an increased signal intensity on T2-weighted sequence image. These lesions were enhanced when a contrast medium was used. The patient underwent open biopsy and specimens were collected through the right pedicle. RESULTS: Diagnosis was established on the basis of direct identification of the microorganism. Histological findings were consistent with examination of B. pickettii spondylitis. Chemotherapy (intravenous cefepime and per os minocycline) resulted in complete cure. CONCLUSION: B. pickettii is widely distributed in aqueous sources in nature and has not previously been considered to be an aggressive pathogen towards humans. This case report will help to improve our understanding of the ecology and virulent pathogenicity of this organism. A biopsy is an essential and reliable method for the early etiologic diagnosis, which will lead to prevent the development of more severe complications such as spinal cord compression.

Burkholderia Infections↗

Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults.

A novel factor, termed Humanin (HN), antagonizes against neurotoxicity by various types of familial Alzheimer's disease (AD) genes [V642I and K595N/M596L (NL) mutants of amyloid precursor protein (APP), M146L-presenilin (PS) 1, and N141I-PS2] and by Abeta1-43 with clear action specificity ineffective on neurotoxicity by polyglutamine repeat Q79 or superoxide dismutase 1 mutants. Here we report that HN can also inhibit neurotoxicity by other AD-relevant insults: other familial AD genes (A617G-APP, L648P-APP, A246E-PS1, L286V-PS1, C410Y-PS1, and H163R-PS1), APP stimulation by anti-APP antibody, and other Abeta peptides (Abeta1-42 and Abeta25-35). The action specificity was further indicated by the finding that HN could not suppress neurotoxicity by glutamate or prion fragment. Against the AD-relevant insults, essential roles of Cys(8) and Ser(14) were commonly indicated, and the domain from Pro(3) to Pro(19) was responsible for the rescue action of HN, in which seven residues turned out to be essential. We also compared the neuroprotective action of S14G HN (HNG) with that of activity-dependent neurotrophic factor, IGF-I, or basic FGF for the antagonism against various AD-relevant insults (V642I-APP, NL-APP, M146L-PS1, N141I-PS2, and Abeta1-43). Although all of these factors could abolish neurotoxicity by Abeta1-43, only HNG could abolish cytotoxicities by all of them. HN and HN derivative peptides may provide a new insight into the study of AD pathophysiology and allow new avenues for the development of therapeutic interventions for various forms of AD.

Alzheimer Disease↗

A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta.

Through functional expression screening, we identified a gene, designated Humanin (HN) cDNA, which encodes a short polypeptide and abolishes death of neuronal cells caused by multiple different types of familial Alzheimer's disease genes and by Abeta amyloid, without effect on death by Q79 or superoxide dismutase-1 mutants. Transfected HN cDNA was transcribed to the corresponding polypeptide and then was secreted into the cultured medium. The rescue action clearly depended on the primary structure of HN. This polypeptide would serve as a molecular clue for the development of new therapeutics for Alzheimer's disease targeting neuroprotection.

Alzheimer Disease↗

Inductive signals from the somatopleure mediated by bone morphogenetic proteins are essential for the formation of the sternal component of avian ribs.

The posterior five pairs of avian ribs are composed of vertebral and sternal components, both derived from the somitic mesoderm. For the patterning of the rib cartilage, inductive signals from neighboring tissues on the somitic mesoderm have been suggested to play critical roles. The notochord and surface ectoderm overlying the somitic mesoderm are essentially required for the development of proximal and distal regions of the ribs, respectively. Involvement of the somatopleure in rib development has already been suggested but is less understood than those of the notochord and surface ectoderm. In this study, we reinvestigated the role of the somatopleure during rib development. We first identified the chicken homologue of the mouse Mesenchymal forkhead-1 (cMfh-1) gene based on sequence similarities. cMfh-1 was observed to be expressed in the nonaxial mesoderm, including the somitic mesoderm, and, subsequently, in cartilage forming the ribs, vertebrae, and appendicular skeletal system. In the interlimb region, corresponding to somites 21-25 (or 26), cMfh-1-positive somitic mesoderm was seen penetrating the somatopleure of E4 embryos, and cMfh-1 was used as a molecular marker demarcating prospective rib cartilage. A series of experiments affecting the penetration of the somitic mesoderm into the somatopleure was performed in the present study, resulting in defects in sternal rib formation. The inductive signals emanating from the somatopleure mediated by BMP family proteins were observed to be essentially involved in the ingrowth of the somitic mesoderm. BMP4 alone, however, could not completely replace inductive signals from the somatopleure, suggesting the involvement of additional signals for rib formation.

Amino Acid Sequence↗

Secreted Abeta does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein.

Antibodies against APP, a precursor of Abeta deposited in Alzheimer's disease brain, have been shown to cause neuronal death. Therefore, it is important to determine whether Abeta mediates antibody-induced neurotoxicity. When primary neurons were treated with anti-APP antibodies, Abeta40 and Abeta42 in the cultured media were undetectable by an assay capable of detecting 100 nM Abeta peptides. However, exogenously treated Abeta1-42 or Abeta1-43 required >3 microM to exert neurotoxicity, and 25 microM Abeta1-40 was not neurotoxic. Glutathione-ethyl-ester inhibited neuronal death by anti-APP antibody, but not death by Abeta1-42, whereas serum attenuated toxicity by Abeta1-42, but not by anti-APP antibody. Using immortalized neuronal cells, we specified the domain responsible for toxicity to be cytoplasmic His(657)-Lys(676), but not the Abeta1-42 region, of APP. This indicates that neuronal cell death by anti-APP antibody is not mediated by secreted Abeta.

Alzheimer Disease↗

Expression of the Dan gene during chicken embryonic development.

The Dan gene was first identified as the putative rat tumor suppressor gene and encodes a protein structurally related to Cerberus and Gremlin in vertebrates. Xenopus DAN, as with Cerberus and Gremlin, was demonstrated to block bone morphogenetic protein (BMP) signaling by binding BMPs, and to be capable of inducing additional anterior structures by ectopic overexpression in Xenopus embryos. DAN, thus, is suggested to play pivotal roles in early patterning and subsequent organ development, as in the case of other BMP antagonists. In this report, we isolated the chicken counterpart of Dan. Chicken Dan is mainly expressed in the cephalic and somitic mesoderm and several placodes during organ development.

Amino Acid Sequence↗

Antibody-regulated neurotoxic function of cell-surface beta-amyloid precursor protein.

APP is a transmembrane precursor of beta-amyloid, and its mutations cause early-onset familial Alzheimer's disease. We report a toxic function of normal wild-type APP (wtAPP). Treatment of neuronal F11 cells, immortalized embryonic day 13 neurons, overexpressing wtAPP with anti-APP antibodies caused death. Death was not induced by antibody in parental F11 cells. Death by antibody occurred through cell-surface APP, not through secreted APP, in a pertussis toxin-sensitive manner and was typical apoptosis, not observed in primary astrocytes or glioma cells overexpressing wtAPP, but observed in primary cortical neurons. Cell-surface APP thus performs a toxic function as an extracellularly controllable regulator of neuronal death. This study provides a novel insight into the normal and pathological functions of cell-surface wtAPP.

Alzheimer Disease↗

Megastigmane, benzyl and phenethyl alcohol glycosides, and 4,4'-dimethoxy-beta-truxinic acid catalpol diester from the leaves of Premna subscandens MERR.

Extensive isolation work on the n-BuOH-soluble fraction obtained from the leaves of Premna subscandens, collected on Ishigaki island, Okinawa, afforded six compounds. Two were identified as megastigmane glucosides, 7-(3,5-dihydroxy-1,1,5-trimethylcyclohexylidene)-9-methylprop++ +-8-enyl 9-O-beta-D-glucopyranoside and 3-hydroxy-5,6-epoxy-beta-ionol 9-O-beta-D-glucopyranoside. The structures of the remaining four new compounds were elucidated to be a 2'-O-beta-D-apiofuranosyl derivative of 3-hydroxy-5,6-epoxy-beta-ionol 9-O-beta-D-glucopyranoside, named premnaionoside, benzyl alcohol beta-D-(2'-O-beta-D-xylopyranosyl)glucopyranoside, phenethyl alcohol beta-D-(2'-O-beta-D-glucopyranosyl)glucopyranoside, and 4,4'-dimethoxy-beta-truxinic acid catalpol diester by spectroscopic analyses.

Acetylation↗

Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferation of sclerotome cells during the vertebral column development.

During axial skeleton development, the notochord is essential for the induction of the sclerotome and for the subsequent differentiation of cartilage forming the vertebral bodies and intervertebral discs. These functions are mainly mediated by the diffusible signaling molecule Sonic hedgehog. The products of the paired-box-containing Pax1 and the mesenchyme forkhead-1 (Mfh1) genes are expressed in the developing sclerotome and are essential for the normal development of the vertebral column. Here, we demonstrate that Mfh1 like Pax1 expression is dependent on Sonic hedgehog signals from the notochord, and Mfh1 and Pax1 act synergistically to generate the vertebral column. In Mfh1/Pax1 double mutants, dorsomedial structures of the vertebrae are missing, resulting in extreme spina bifida accompanied by subcutaneous myelomeningocoele, and the vertebral bodies and intervertebral discs are missing. The morphological defects in Mfh1/Pax1 double mutants strongly correlate with the reduction of the mitotic rate of sclerotome cells. Thus, both the Mfh1 and the Pax1 gene products cooperate to mediate Sonic hedgehog-dependent proliferation of sclerotome cells.

Animals↗

An international study of patient compliance with hemodialysis.

CONTEXT: International differences in compliance of patients undergoing hemodialysis are poorly characterized and could contribute to international survival differences. OBJECTIVE: To compare international differences in patient compliance with hemodialysis treatments. DESIGN: A prospective observational study of patients undergoing hemodialysis in 1995 and a cross-sectional survey of health care professionals caring for hemodialyzed patients in 1996. SETTING AND PATIENTS: Four dialysis centers in the southeastern United States with 415 patients undergoing hemodialysis, 1 center in Sweden with 84 patients, and 4 centers in Japan with 194 patients participated in the prospective observational study. In the cross-sectional survey, nurses and nephrologists from the United States (n = 49), Japan (n = 21), and Sweden (n = 16) responded to questions regarding the compliance of their patients undergoing hemodialysis. MAIN OUTCOME MEASURES: Percentage of patients who miss a dialysis treatment and number of missed dialysis treatments. RESULTS: Of 415 US patients, 147 missed 699 treatments over a 6-month period (28.1 missed treatments per 100 patient-months or 2.3% of all prescribed treatments). During a 3-month period, there were 0 missed treatments per 100 patient-months for patients from Japan and 0 missed treatments per 100 patient-months for patients from Sweden (P<.001). In the cross-sectional survey, the mean (SD) estimated percentage of patients missing a treatment per month was 4% (3%) for the United States, 0% for Japan, and 0.1% (3%) for Sweden (P<.001). CONCLUSIONS: Noncompliance is much more common in US patients undergoing hemodialysis than Swedish and Japanese patients. The implications of these results for international differences in survival deserve further study.

Cross-Sectional Studies↗

Hemodynamic and hormonal responses to nicorandil in a canine model of acute ischemic heart failure: a comparison with cromakalim and nitroglycerin.

The pharmacologic profiles of nicorandil in the cardiovascular system have been characterized by K-channel opening and nitrate activities. However, the effects of nicorandil on acute heart failure have yet to be elucidated. To investigate the effects of nicorandil under such pathophysiologic conditions, we administered nicorandil intravenously to dogs with acute ischemic heart failure induced by coronary embolization and compared the results with those induced by cromakalim and nitroglycerin. The heart failure in this experiment was demonstrated by a reduction of mean blood pressure (MBP) from 143+/-3 to 129+/-2 mm Hg (p < 0.01); cardiac output (CO) from 2.18+/-0.10 to 1.06+/-0.05 L/min (p < 0.01); stroke volume (SV) from 12.7+/-0.6 to 6.8+/-0.3 ml/min (p < 0.01); Vmax, an index of the contractility of the left ventricle, from 105.5+/-4.4 to 49.9+/-1.8 1/s (p < 0.01), and an increase in right atrial pressure (RAP) from 2.9+/-0.3 to 5.3+/-0.3 mm Hg (p < 0.01); left ventricular end-diastolic pressure (LVEDP) from 2.5+/-0.4 to 26.0+/-1.4 mm Hg (p < 0.01); and T, time constant of left ventricular relaxation, from 38.3+/-0.8 to 62.4+/-2.8 ms (p < 0.01). Furthermore, plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP) increased (from 1.72+/-0.29 to 5.03+/-0.68 ng AngI/ml/h, p < 0.01; from 103.9+/-5.8 to 411.5+/-29.4 pg/ml, p < 0.01, respectively), whereas brain natriuretic peptide (BNP) remained unchanged (from 23.1+/-2.2 to 26.9+/-1.4 pg/ml). Nicorandil (10-40 microg/kg/min, i.v. infusion for 20 min for each dosing) or cromakalim (0.25-1 microg/kg/min) decreased MBP, systemic vascular resistance (SVR), RAP, and LVEDP, and increased CO, SV, and Vmax. However, the reduction of RAP in cromakalim was significantly smaller than those of nicorandil and nitroglycerin in comparison at similar hypotensive doses. Nitroglycerin (2.5-10 microg/kg/min) decreased MBP, RAP, and LVEDP, and increased Vmax but did not change CO or SV. Increased plasma ANP levels, an index of cardiac filling pressure after induction of acute ischemic heart failure, were decreased significantly by cromakalim and tended to decrease by nicorandil or nitroglycerin. Plasma BNP levels and PRA were not influenced by any of these drugs. These results suggest that nicorandil produces the reduction of both preload and afterload followed by an improvement of cardiac contractility in this model. The increase in CO may be mediated mainly by the drug's K-channel opening activities and the reduction of venous tone by its nitrate properties. Nicorandil may prove to be useful in the treatment of acute ischemic heart failure.

Acute Disease↗

A collagen network formation effector from leaves of Premna subscandens.

As a part of the search for biologically active plant products, M cells, which form a collagen fiber network in vitro after a prolonged culture period, were used. The n-BuOH-soluble fraction of a methanol extract of leaves of Premna subscandens exhibited promotion of collagen network formation by M cells. Extensive isolation work guided by a bioassay afforded a phenylethanoid, acteoside, as an active compound.

Cell Line↗

Eosinophilic pustular folliculitis effectively treated with recombinant interferon-gamma: suppression of mRNA expression of interleukin 5 in peripheral blood mononuclear cells.

Eosinophilic pustular folliculitis (EPF) is characterized clinically by pruritic grouped follicular papules and pustules on the trunk, limbs, and face, and, histologically, by follicular infiltration with eosinophils. The blood eosinophil count is elevated in most patients. Oral minocycline, nonsteroidal anti-inflammatory drugs, diaminodiphenylsulphone, and corticosteroids may induce remission. We report two Japanese men with EPF who responded poorly to the usual therapy. Intravenous injections of recombinant interferon-gamma (rIFN-gamma), 5 x 10(5) to 2 x 10(6) Japan Reference Unit (JRU) (1 JRU roughly corresponds to 4 NIH units) daily for 7 days, cleared the skin lesions and returned the peripheral eosinophil counts to normal in both patients. However, the lesions recurred 2-3 days after rIFN-gamma was stopped. Both patients have received intravenous rIFN-gamma once or twice a week for nearly 1 year without systemic side-effects. Reverse transcriptase-polymerase chain reaction revealed a decreased expression of interleukin 5 (IL-5) mRNA in peripheral mononuclear cells after the rIFN-gamma therapy. rIFN-gamma may become the treatment of choice in recalcitrant EPF, although further studies are needed. It may work by interfering with the immunological function of type 2 T-helper cells, including IL-5 production responsible for the growth and differentiation of eosinophils.

Adult↗

Reperfusion at reduced flow rates enhances postischemic contractile recovery of perfused heart.

The effects of reperfusion at reduced flow rates on postischemic cardiac contractile function were examined in perfused rat hearts. Isolated hearts were subjected to 35-min ischemia followed by reperfusion at the preischemic flow rate (9.0 ml.g-1.min-1; ordinary flow rate) or at reduced flow rates (0.9-8.1 ml.g-1.min-1). Reperfusion at ordinary flow rate did not generate any left ventricular developed pressure (LVDP), whereas reperfusion at reduced flow rates (0.9-7.2 ml.g-1.min-1) elicited 13-57% of initial contractile force at reperfusion's end; optimal recovery occurred at 3.6 ml.g-1.min-1 (reduced flow rate). Reduced flow rate reperfusion attenuated ischemia-reperfusion-induced increase in left ventricular end-diastolic pressure (LVEDP) and perfusion pressure (PP), alteration in tissue Na+, K+, Ca2+, and Mg2+, release of creatine kinase and ATP metabolites, and development of triphenyltetrazolium chloride-unstained areas. Enhanced postischemic LVDP recovery was inversely related to higher coronary PP at the initial stage (4 min) of reperfusion (r = -0.763). The benefit of reduced flow rate reperfusion could not be attributed to rate of calcium delivery to the heart, formation of oxygen free radicals in myocardium, endothelium-dependent coronary artery dilation, or LVDEP reduction. Enhancement of postischemic LVDP recovery was associated with attenuation of ischemia-reperfusion-induced increases in myocardial sodium and calcium; failure of postischemic LVDP recovery was accompanied by an increase. Reduction in sodium and calcium overload may underlie the beneficial effects of reduced flow rate reperfusion in ischemic-reperfused heart.

Adenosine Triphosphate↗

Cytokeratin fragment 21-1 in gynecologic malignancy: comparison with cancer antigen 125 and squamous cell carcinoma-related antigen.

We measured serum cytokeratin fragment 21-1 (CYFRA 21-1) levels by a solid-phase immunoradiometric assay in 102 healthy Japanese women, and set the reference value at 1.9 ng/ml (mean +2 SD of the serum levels based on a linear distribution). Pretreatment serum CYFRA 21-1 levels were also analyzed in 235 women with benign (n = 94) or malignant (n = 141) gynecologic disease, and were compared with the serum levels of CA 125 and SCC. The respective positivity rates for CYFRA 21-1 and CA 125 were 64.0 and 77.2% in ovarian malignancy, while they were 4.2 and 30.8% in benign ovarian masses. CYFRA 21-1 had an accuracy of 61.3% in diagnosing ovarian malignancy, which was higher than that of CA 125 (53.4%). The positive predictive value of CYFRA 21-1 for ovarian malignancy reached 94.1%, which was significantly (p < 0.005) higher than that of CA 125 (68.8%). These findings indicate the potential usefulness of CYFRA 21-1 as a tumor marker for ovarian malignancy. In addition, the positivity rates fo CYFRA 21-1 in cervical cancer (51.2%) and endometrial cancer (52.2%) were also similar to the respective rates for SCC and CA 125, which suggests that CYFRA 21-1 seems to be a general tumor marker for gynecologic malignancy.

Adolescent↗

Immunoradiometrical measurement of tissue polypeptide specific antigen (TPS) in normal, healthy, nonpregnant and pregnant Japanese women.

Using a monoclonal immunoradiometrical assay, we measured the concentrations of the specific epitope M3 of tissue polypeptide antigen (TPA), namely, tissue polypeptide specific antigen (TPS), in serum and amniotic fluid obtained from normal, healthy, nonpregnant and pregnant Japanese women (NHNJW and NHPJW). The cut-off value of the serum TPS level was set at 130 U/l, based on the mean +2 standard deviations in the NHNJW. The serial measurement of serum TPS levels demonstrated the significant temporal elevation of TPS level near the time of ovulation (+/- 3 days) in the ovulatory women. In the NHPJW, the mean serum TPS level and the positivity rate (> 130 U/l) increased with the advance of gestation, reaching 183.7 U/l and 66.7%, respectively, in the third trimester. Maternal serum levels were much elevated just before (mean: 982.3 U/l) and after (mean: 824.6 U/l) delivery, and were reduced to about one-fourth by 3 days. In addition, markedly high TPS concentrations were found in the retroplacental blood (one case: 9,076 U/l) and the amniotic fluid (mean: 11,650 U/l). The serum TPS level correlated well (r = 0.871) with the serum TPA level in the TPS range of 2-2,000 U/l, while a poor correlation (r = 0.273) was found in the TPS range of 2-500 U/l. The present study thus obtained fundamental data on TPS in Japanese women. The fluctuation and change of serum TPS levels during the menstrual cycle and in pregnancy should be taken into consideration when we apply TPS as a tumor marker for women.

Adolescent↗

[Innervation of the external ear in humans and the musk shrew].

The external ear appears only in mammals and possesses a great diversity of forms. In addition, multiple nerves are distributed in the external ear. The nerves which are distributed in the external ear were investigated in humans and in the musk shrew (Suncus murinus) in a macroscopic study. The following results were obtained. Cranial nerves (CN) V, VII, X and cervical nerves supply the auricle and the external meatus in both humans and the musk shrew. Branches of the third division of CN V supply an anterior part of the external meatus and the anterior part of the auricle in both humans and the musk shrew. A branch of CN X, together with a branch of CN VII, supply the posterior parts of the external meatus in humans. In the musk shrew, a branch of CN X, together with a branch of CN VII, supplies the posterior part of the external meatus and the central part and the anterior portion of the auricle. Branches of the cervical nerve supply the posterior part of the auricle. Branches of the cervical nerve supply the posterior part of the external meatus and the central and posterior parts of the auricle in the musk shrew.

Aged↗