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Biomedical subjects

S Shoji

Publications and source records attributed to S Shoji.

At least 19 recordsLinked to original sources

IL-18 gene polymorphism confers susceptibility to the development of anti-GAD65 antibody in Graves' disease.

AIMS: This study aimed to investigate whether interleukin-18 (IL-18) gene polymorphisms are associated with the development of antibody against the 65-kDa isoform of recombinant human glutamic acid decarboxylase (GAD65Ab) in patients with Graves' disease. METHODS: A total of 398 unrelated Japanese patients with Graves' disease, with and without GAD65Ab, were recruited. Three single nucleotide polymorphisms in the IL-18 gene were examined and the polymorphic allele and the genotype and haplotype frequencies calculated. RESULTS: The frequency of the GG genotype at position -4675 of the IL-18 gene was significantly lower in Graves' disease patients with GAD65Ab than those without (4% vs. 24%, P = 0.0126). The -4675C allele frequency was significantly greater in patients with GAD65Ab than those without (69% vs. 53%, P = 0.0168). The homozygous -4675G/-607A/-137G haplotype was less common in Graves' disease patients with GAD65Ab than those without (4% vs. 23%, P = 0.0144). CONCLUSIONS: These findings in a Japanese population indicate that Graves' disease patients carrying the GG genotype at position -4657 of the promoter of the IL-18 gene or a gene in linkage disequilibrium with the -4675G/-607A/-137G haplotype have a low risk for the development of GAD65Ab in Graves' disease.

Adolescent↗

[Small peripheral lung cancer incidentally detected by massive hemoptysis].

A 47-year-old man was admitted to our hospital for treatment of massive hemoptysis. He was intubated and underwent bronchial arterial embolization because of this deteriorating respiratory state and uncontrollable hemoptysis. Computed tomography (CT) of the chest showed a 1-cm nodular shadow in the peripheral apical lobe (S1) of the right lung. He underwent right upper lobectomy for the purpose of preventing re-hemorrhage as well as making the definitive diagnosis of nodular shadow in S1 of the right lung. Intraoperative pathological examination revealed the nodule as adenocarcinoma, and mediastinal lymphadenectomy was added to the right upper lobectomy. The patient recovered uneventfully, and there has been no sign of recurrence for 15 months after the operation.

Adenocarcinoma↗

[Metastatic lung tumor from uterine leiomyosarcoma].

We herein present 2 cases of metastatic lung tumor derived from uterine leiomyosarcoma. In the case 1, a 59-year-old woman was admitted to our hospital to examine abnormal shadow detected on chest X-ray. She had undergone hysterectomy and oophorectomy for uterine leiomyosarcoma 19 months previously. A round 3 cm mass in the right lung (S10) was seen on chest X-ray and computed tomography (CT). No other distant metastases or local recurrence were found, and the right lower lobectomy was perfomed under the clinical diagnosis of metastatic lung tumor. Postoperative pathologic examination revealed the tumor as a metastatic leiomyosarcoma. The patient recovered uneventfully, and there have been no signs of recurrence for 26 months after the pulmonary resection. In the case 2, a 58-year-old woman, who had undergone hysterectomy and oophorectomy for uterine leiomyosarcoma 7 months previously, was admitted to our hospital for further examination of pulmonary tumors on chest X-ray. Two tumors were recognized in the left lung (S8 and S10) on chest X-ray and CT. No other distant metastases or local recurrence were found, and the left lower lobectomy was performed under the clinical diagnosis of metastatic lung tumors. Pathological examinations revealed smooth muscle cells with nuclear pleomorphism and high mitotic indices. The tumors proved to be lung metastases derived from uterine leiomyosarcoma. Postoperative course was uneventful. However, brain metastasis was found 1 month after the pulmonary resection, and she underwent resection of brain metastasis. Two months after the brain metastasectomy, local recurrence of the brain tumor developed and re-resection followed by stereotactic radiotherapy was performed. Furthermore, intrapelvic recurrence was found 4 months after the pulmonary resection. Exploratory laparotomy revealed the tumor was unresectable, and she received 4 courses of chemotherapy (paclitaxel and carboplatin). For metastatic lung tumor from uterine leiomyosarcoma, surgery has been considered the best choice. However, for patients with uterine leiomyosarcoma who cannot be treated surgically because of multiple metastatic tumors or poor surgical risk chemotherapy (paclitaxel and carboplatin) or stereotactic radiotherapy can be strategies.

Antineoplastic Combined Chemotherapy Protocols↗

Acute flank pain, an unusual first symptom of a spinal arteriovenous malformation.

This case report describes a 46-year-old man whose first symptom was an attack of acute flank pain, followed by the gradual onset neurological symptoms. We demonstrated a small nidus and serpentine signal-void area in the spinal cord by MRI and diagnosed a glomus type of spinal arteriovenous malformation (AVM). Flank pain is a rare initial finding in an adult with spinal AVM. In cases with acute flank pain, neurologists should consider spinal AVM as a differential diagnosis.

Angiography↗

CSF hypocretin levels in Guillain-Barré syndrome and other inflammatory neuropathies.

CSF hypocretin-1 was measured in 28 Guillain-Barré syndrome (GBS), 12 Miller-Fisher syndrome, 12 chronic inflammatory demyelinating polyneuropathy (CIDP), and 48 control subjects. Seven GBS subjects had undetectably low hypocretin-1 levels (<100 pg/mL). Hypocretin-1 levels were moderately reduced in an additional 11 GBS, 5 Miller-Fisher syndrome, and 1 CIDP subject. Low levels in GBS occurred early in the disease and were associated with upper CNS level abnormalities.

Adolescent↗

Progressive supranuclear palsy presenting with primary progressive aphasia--clinicopathological report of an autopsy case.

We report a Japanese autopsy case of progressive supranuclear palsy (PSP). The male patient was 74 years old at the time of death. At age 64, he developed non-fluent aphasia that progressed slowly over 8 years, eventually associated with behavioral abnormality, postural instability, and dysphagia at 2 years prior to his death. Magnetic resonance imaging of the brain at age 73 demonstrated marked atrophy of the frontal lobes, particularly on the left side. Neuropathological examination revealed the typical pathology of PSP: loss of neurons, gliosis, occurrence of neurofibrillary tangles, oligodendroglial coiled bodies, and tuft-shaped astrocytes in the frontal cortex, associated with argyrophilic threads in the underlying white matter, in the basal ganglia, including the thalamus, globus pallidus, and subthalamic nucleus, and in the brainstem nuclei, including the substantia nigra, pontine nucleus, and inferior olivary nucleus. No astrocytic plaques or ballooned neurons were observed. Protein analysis revealed accumulation of hyperphosphorylated tau of 68 and 64 kDa consisting of the four repeat tau isoforms. We conclude that the present case represented PSP with an 8-year history of primary progressive aphasia (PPA). Although focal cortical symptoms in PSP are rare or absent, we should keep in mind the possibility of atypical PSP in which cortical pathology is predominant, particularly in the frontal lobe, and could result in PPA.

Aged↗

Association between catechol-O-methyltransferase gene polymorphisms and wearing-off and dyskinesia in Parkinson's disease.

Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines, including levodopa. An amino acid change (Val-108-Met) in the COMT protein has been found to result in a change from high to low enzyme activity. In the present study, we genotyped 121 Japanese patients with Parkinson's disease (PD) and 100 controls. Comparison of the allele frequencies revealed that homozygosity for the low-activity allele was significantly more common among PD patients than the controls (p = 0.047, odds ratio = 3.23). In addition, homozygosity for the low-activity allele was overrepresented in PD patients that exhibited the 'wearing-off' phenomenon (p = 0.045, odds ratio = 3.82) or dyskinesia (p = 0.030, odds ratio = 4.80) compared with controls, although these differences were not significant after Bonferroni's correction. Our results may help understand the mechanism that cause complications of levodopa therapy in PD patients.

Aged↗

Characterization of Ca(2+) signaling pathways in human mesenchymal stem cells.

Human mesenchymal stem cells (HMSC) have the potential to differentiate into many cell types. The physiological properties of HMSCs including their Ca(2+) signaling pathways, however, are not well understood. We investigated Ca(2+) influx and release functions in HMSCs. In Ca(2+) imaging experiments, spontaneous Ca(2+) oscillations were observed in 36 of 50 HMSCs. The Ca(2+) oscillations were completely blocked by the application of 10 micro M cyclopiazonic acid (CPA) or 1 micro M thapsigargin (TG). A brief application of 1 micro M acetylcholine (ACh) induced a transient increase of [Ca(2+)](i) but the application of caffeine (10 mM) did not induce any Ca(2+) transient. When the stores were depleted with Ca(2+)-ATPase blockers (CPA or TG) or muscarinic agonists (ACh), store-operated Ca(2+) (SOC) entry was observed. Using the patch-clamp technique, store-operated Ca(2+) currents (I(SOC)) could be recorded in cells treated with ACh or CPA, but voltage-operated Ca(2+) currents (VOCCs) were not elicited in most of the cells (17/20), but in 15% of cells examined, small dihydropyridine (DHP)-sensitive Ca(2+) currents were recorded. Using RT-PCR, mRNAs were detected for inositol 1,4,5-trisphosphate receptor (InsP(3)R) type I, II, and III and DHP receptors alpha1A and alpha1H were detected, but mRNA was not detected for ryanodine receptor (RyR) or N-type Ca(2+) channels. These results suggest that in undifferentiated HMSCs, Ca(2+) release is mediated by InsP(3)Rs and Ca(2+) entry through plasma membrane is mainly mediated by the SOCs channels with a little contribution of VOCCs.

Calcium↗

Down-regulation of N-myristoyl transferase expression in human T-cell line CEM by human immunodeficiency virus type-1 infection.

The present study focuses on the expression level of N-myristoyl transferase (NMT) in the course of human immunodeficiency virus type-1 (HIV-1) infection. HIV-1 structural proteins were gradually expressed during the process of infection of the human T-cell line CEM, whereas the expression levels of NMT subsequently decreased under the same conditions. In addition, the chronically HIV-1-infected T-cell line CEM/LAV-1 exhibited low expression levels of NMT. We hypothesize that the decrease in the expression level of NMT due to HIV-1 infection may be related to the virus' strategy that leads to its persistent replication.

Acyltransferases↗

Differential nociceptive responses in mice lacking the alpha(1B) subunit of N-type Ca(2+) channels.

The role of N-type Ca(2+) channels in nociceptive transmission was examined in genetically engineered mice lacking the alpha(1B) subunit of N-type channels and in their heterozygote and wild-type littermates. In alpha(1B)-deficient mice, N-type channel activities in dorsal root ganglion neurons and spinal synaptoneurosomes were eliminated without compensation by other types of voltage-dependent Ca(2+) channels. The alpha(1B)-deficient mice showed a diminution in the phase 2 nociceptive responses more extensively than in the phase 1 nociceptive responses of the formalin test. The alpha(1B)-deficient mice exhibited significantly increased thermal nociceptive thresholds in the hot plate test, but failed to increase mechanical nociceptive thresholds in the tail pinch test. These results suggest a crucial role of N-type channels in nociceptive transmission, especially for persistent pain like phase 2 of the formalin test and for nociception induced by thermal stimuli.

Animals↗

Evidence as a HIV-1 self-defense vaccine of cyclic chimeric dodecapeptide warped from undecapeptidyl arch of extracellular loop 2 in both CCR5 and CXCR4.

Novel conformation-specific antibodies were raised against a cyclic chimeric dodecapeptidyl multiple antigen peptide (cCD-MAP) constructed with a spacer-armed Gly-Asp dipeptide and two pentapeptides (S(169)-Q(170)-K(171)-E(172)-G(173) of CCR5 and E(179)-A(180)-D(181)-D(182)-R(183) of CXCR4) which are components of the undecapeptidyl arch (UPA: from R(168) to C(178) in CCR5, from N(176) to C(186) in CXCR4) of extracellular loop 2 (ECL2) in chemokine receptors (CCR5 and CXCR4). Of the antibodies raised, one monoclonal antibody, CPMAb-I (IgMkappa), reacted with cCD-MAP, but not with the linear chimeric dodecapeptide-MAP. The antibody reacted with the cells separately expressing CCR5 or CXCR4, but not with those not expressing the coreceptors. Moreover, the antibody markedly suppressed infection by X4, R5, or R5X4 virus in a dose-dependent manner in a new phenotypic assay for drug susceptibility of HIV-1 using CCR5-expressing Hela/CD4(+) cell clone 1-10 (MAGIC-5). Moreover, CPMAb-I interfered with LAV-1(BRU) infection (m.o.i. = 0.01) of Molt4#8 cells cocultured with CPMAb-I-producing hybridoma in the transwell, and significantly interfered with neither chemotaxis nor calcium influx induced with stromal cell-derived factor 1 alpha (SDF-1alpha). Thus, the antibody raised against the cCD-MAP provides powerful protection or defense against HIV-1 infection. We therefore propose the cCD-MAP or its derivative immunogen as a novel candidate for an HIV-1 coreceptor-based self-defense vaccine.

AIDS Vaccines↗

Variant transthyretin in blood circulation can transverse the blood-cerebrospinal barrier: qualitative analyses of transthyretin metabolism in sequential liver transplantation.

BACKGROUND: Although the choroid6 plexus of the brain is one of the most important production sites of transthyretin (TTR), the metabolism of TTR secreted in cerebrospinal fluid (CSF) remains to be elucidated. METHODS: To perform qualitative analysis of variant TTR in CSF of patients who underwent a sequential liver transplantation using an explanted familial amyloidotic polyneuropathy (FAP) ATTR Val30 Met patient's liver, levels and forms of TTR of the two patients were analyzed by means of enzyme linked immunosorbent assay (ELISA) and matrix-assisted laser desorption/time-of-flight mass spectrometer (MALDI/TOF-MS), respectively. RESULTS: After the operation, variant TTR levels in serum increased, and in CSF, a significant peak of free form of ATTR Val30 Met was detected in the transplanted patients whose CSF had shown no variant TTR before the operation. CONCLUSIONS: These findings suggest that the variant TTR can cross-the blood-CSF barrier and migrate into CSF from blood circulation. Because leptomeningeal amyloidosis occurs in FAP ATTR Val30 Met as the progression of the disease, this information suggests that in addition to peripheral neuropathy, disorders of the central nervous system (CNS) should be given an attention in patients who underwent sequential liver transplantation using an explanted FAP ATTR Val30 Met patient's liver.

Adolescent↗

Cytoplasmic and nuclear polyglutamine aggregates in SCA6 Purkinje cells.

Aggregations of the alpha1A-calcium channel protein have been previously demonstrated in spinocerebellar ataxia type 6 (SCA6). Here the authors show that small aggregates, labeled by a monoclonal antibody 1C2 that preferentially detects expanded polyglutamine larger than that in SCA6 mutation, are present mainly in the cytoplasm but also in the nucleus of Purkinje cells. Although the length of expansion is small in SCA6, the current finding might indicate that SCA6 conforms to the pathogenic mechanism(s) in other polyglutamine diseases.

Brain↗