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Biomedical subjects

M Nakazawa

Publications and source records attributed to M Nakazawa.

At least 55 records · Page 3Linked to original sources

Serodiagnosis of chronic Chagas infection by using EIE-Recombinant-Chagas-Biomanguinhos kit.

A kit based on an enzyme immunoassay, EIE-Recombinant-Chagas-Biomanguinhos, developed by the Oswaldo Cruz Foundation, was evaluated for the serodiagnosis of chronic Chagas disease. Evaluation was performed with 368 serum samples collected from individuals living in an endemic area for Chagas disease: 131 patients in the chronic phase with confirmed clinical, epidemiological, and serological diagnosis (indirect immunofluorescence, indirect hemagglutination or enzyme-linked immunosorbent assay) and 237 nonchagasic seronegative individuals were considered negative control. The EIE-Recombinant-Chagas-Biomanguinhos kit showed high sensitivity, 100% (CI 95%: 96.4-100%) and high specificity, 100% (CI 95%: 98-100%). The data obtained were in full agreement with clinical and conventional serology data. In addition, no cross-reaction was observed with sera from patients with cutaneous (n=14) and visceral (n=3) leishmaniasis. However, when these sera were tested by conventional serological assays for Chagas disease, cross-reactions were detected in 14.3% and 33.3% of the patients with cutaneous and visceral leishmaniasis, respectively. No cross-reactions were observed when sera from nonchagasic seronegative patients bearing other infectious disease (syphilis, n=8; HTLV, n=8; HCV, n=7 and HBV, n=12) were tested. In addition, sera of patients with inconclusive results for Chagas disease by conventional serology showed results in agreement with clinical evaluation, when tested by the kit. These results are relevant and indicate that the referred kit provides a safe immunodiagnosis of Chagas disease and could be used in blood bank screening.

Adolescent↗

Normal tension glaucoma and primary open angle glaucoma associated with increased platelet aggregation.

On purpose of the present study was to evaluate platelet aggregation and fibrinolytic systems in patients with normal tension glaucoma (NTG) or primary open angle glaucoma (POAG). For platelet aggregation, we photoelectrophotometrically investigated adenosine diphosphate (ADP) or collagen-induced platelet aggregation in consecutively selected patients with glaucoma (22 patients with NTG and 13 patients with POAG) and 42 glaucoma free control subjects with normal ocular findings. The aggregation patterns of the patients' platelets reacted abnormally to ADP 1 microM or collagen 0.5 microg/ml as evidenced by secondary aggregation were compared with those of control subjects. For blood coagulative and fibrinolytic systems, we measured prothrombin time, activated partial thromboplastin time, fibrinogen, thrombin-antithrombin III complex (TAT), alpha2 plasmin inhibitor-plasmin complex. Seventeen of 22 patients (77%) with NTG and 5 of 13 patients (38%) with POAG showed abnormal secondary aggregation. A significant difference was observed between the two groups. No control subjects showed abnormal secondary aggregation. In the fibrinolytic test, all the parameters examined showed within normal ranges, although the log10(TAT) value was higher in NTG than in POAG. Results of the present study suggested that increased platelet aggregation as defined by ADP or collagen induced abnormal secondary aggregation in vitro is frequently associated with glaucoma patients and this tendency is more apparent in NTG than that in POAG.

Adenosine Diphosphate↗

NFkappaB2 (p52) promoter activation via Notch signaling pathway in rheumatoid synoviocytes.

Rheumatoid synoviocytes produce inflammatory cytokines and exhibit strong proliferation activity, which cause severe cartilage destruction in the joints. Previously, we reported that NFkappaB, a transcriptional factor that activated by mitogenic signals, was activated in rheumatoid synoviocytes. In addition, we revealed that Notch-1, the transcriptional factor that is involved in the developmental stages, was abnormally activated in rheumatoid synoviocytes. In this study, as one of the roles of Notch-1 for the chronic inflammation in RA, we examined its implication to NFkappaB2 activation in rheumatoid synoviocytes. Western blotting analysis showed that NFkappaB2 expression was elevated in rheumatoid synoviocytes compared with patients with osteoarthritis studied as control. We then analyzed NFkappaB2 binding activity to the promoter and revealed that kappaB binding complexes to the NFkappaB2 promoter was elevated in rheumatoid synoviocytes. We analyzed implication of Notch-1 signaling pathway on NFkappaB2 activation, and found that Notch-1 made a complex with recombination binding protein Jkappa (RBPJkappa), a repressor for NFkappaB2 promoter, and blocked binding of RBPJkappa to the promoter. These results indicated that as one of the mechanisms for nuclear translocated Notch-1, complex formation with RBPJkappa induces blocking of the NFkappaB2 promoter suppression, which might cause NFkappaB2 promoter activation.

Arthritis, Rheumatoid↗

[Possible pathogenesis of rheumatoid arthritis].

Rheumatoid fibroblast-like synoviocytes characteristically proliferate in an anchorage-independent manner, and are deeply implicated in cartilage destruction. Our previous results showed that rheumatoid synoviocytes expressed Fas ligand and were induced apoptosis by anti-Fas antibody treatment. In addition, several transcriptional factors, such as NF kappa B and AP-1 significantly activated in rheumatoid synoviocytes. We are now clarifying the pathogenesis of RA with the method, yeast two-hybrid system as 'post genome' strategy. We recently found that several factors that related with cell differentiation highly expressed in rheumatoid synoviocytes. In this report we discuss possible pathogenesis of RA based on our recent data and application to the therapy tool against RA.

Apoptosis↗

[Ocular surface changes after dacryocystorhinostomy].

PURPOSE: To observe changes in tear film lipid interference patterns on the ocular surface in patients with nasolacrimal duct (NLD) obstruction before and after dacryocystorhinostomy (DCR). METHODS: The tear film lipid layer on the ocular surface was observed with a specular reflection video recording system in 5 eyes of 4 patients with NLD obstruction before and after DCR. Precorneal tear lipid layer interference patterns at the central cornea, tear meniscus height (TMH), and the Shirmer I test were recorded. Observed patterns were classified into 5 grades. RESULTS: Three of four eyes with TMH values over 0.4 mm before DCR showed decreased TMH postoperatively. One eye with a TMH of 0.2 mm showed no change after DCR. Concerning the tear film lipid layer interference patterns, 4 eyes were classified as grade 1 or 2, and 1 eye was classified as grade 4 before DCR. After DCR, the 5 eyes were classified from grade 3 to grade 4. Epiphora was successfully resolved in all patients after DCR. CONCLUSION: Tear film lipid layers were classified as normal grades before DCR but most cases changed to high grades after DCR. We suggest that the eye after DCR should have a thicker lipid layer than before DCR.

Aged↗

[The histological antitumor effect and side effects of preoperative chemotherapy for patients with oral squamous cell carcinoma--comparison between low-dose and high-dose CDDP regimens].

Preoperative chemotherapy should be effective against cancers and have few side effects that would prevent surgery. We investigated the histological effects and side effects of low- and high-dose CDDP chemotherapy against oral squamous cell carcinoma (SCC), and discuss the therapeutic benefits of each regimen. Thirty-six patients were divided into two groups as follows, in a non-randomized manner: A) low-dose CDDP (17 patients): CDDP 5 mg/m2/day + UFT 400 mg/day (day 1-5) (1 or 2 courses), B) high-dose CDDP (19 patients): CDDP 70-100 mg/m2/day (day 1) + peplomycin 5 mg/day (day 2-6) (1 or 2 courses). Curative surgery was conducted 1 week after protocol A or 2-3 weeks after protocol B. The histological antitumor effects were evaluated with Ohboshi & Shimosato's classification using surgical materials of primary tumors. In this classification, grade IIB, III and IV were as effective. Maximum histological effect was seen with grade IIB for regimen A and grade IV for regimen B. Four of 17 patients (23.5%) responded to regimen A and 13 of 19 patients (68.4%) to regimen B. Side effects, such as nausea, vomiting and myelosuppression, appeared with regimen B, but were seen little with regimen A. The 2-year survival rate was 93.3% with regimen A and 78.9% with regimen B. With regimen A, the 2-year survival rate of effective cases was 100% and that of ineffective cases was 91.7%. With regimen B, the rate was 92.3% and 50.0%, respectively. Effective cases showed good prognosis in both groups. The low-dose CDDP regimen was not so effective against primary tumors histologically, but the prognosis was good. The low-dose CDDP regimen appears to be useful for preoperative chemotherapy of oral SCC.

Antibiotics, Antineoplastic↗

[A case of suspected drug-induced ocular pemphigoid].

BACKGROUND: Lacrimal obstruction can occur as a complication of ocular cicatricial pemphigoid. We report a patient who was diagnosed as having drug-induced ocular cicatricial pemphigoid associated with acquired lacrimal canalicular obstruction in spite of relatively mild subconjunctival scar formation. CASE: The patient was a 69-year-old woman. She had been treated for glaucoma, blepharoconjunctivitis, dacryocystitis, and lacrimal canalicular obstruction for two years with topical administration including 0.5% timolol maleate, 0.1% dipivefrine hydrocholoride, 0.1% fluorometholone, and 0.3% ofloxacin. The patient had moderate conjunctival hyperemia without shortening of the inferior conjunctival sac, corneal ulceration, neovascularization, and keratinization. Lacrimal canalicular obstruction progressed further as topical ocular medications were continued. Topical anti-glaucoma medications were stopped after dacryocystorhinostomy. Although the blepharoconjunctivitis was improved, left inferior conjunctival symblepharon, and medical canthal keratinization was progressive despite the use of topical corticosteroids. The conjunctival biopsy specimen showed the lacrimal punctum covered with proliferated conjunctival epithelium. There was a moderate stromal infiltration of small lymphocytes and plasma cells. We diagnosed this patient as having drug-induced ocular cicatricial pemphigoid caused by topical anti-glaucoma medications. CONCLUSION: Lacrimal canalicular obstructions may occur with the topical anti-glaucoma medications even when subconjunctival scarring is mild.

Aged↗

[Autoimmune mechanisms in molecular pathology of glaucomatous optic neuropathy].

BACKGROUND: Glaucomatous optic neuropathy is characterized by loss of retinal ganglion cells and their axons, excavated appearance of the optic nerve head, and progressive loss of visual field sensitivity. In terms of pathology of the glaucomatous optic neuropathy, observations suggest retinal ganglion cell death by apoptosis. Deprivation of neurotrophic factors, ischemia, chronic elevation of glutamate, and disorganized nitric oxide metabolism have been suspected to be mechanisms triggering apoptosis. Another recent suggestion is that autoantibodies directed toward retinal antigens may be involved in facilitating apoptotic cell death in some glaucoma patients. METHOD: We summarized previous reports dealing with the relationship between glaucoma etiology and autoimmune responses, and investigated the contribution of autoimmune factors in glaucomatous optic neuropathy using electrophysiological and biochemical methods. RESULTS: We found serum anti-neuron specific enolase(NSE) antibody in approximately 20% of our glaucoma patients. In primary open angle glaucoma, maximum and mean intraocular pressures in antibody positive patients were significantly or relatively lower than pressures in antibody negative patients. In addition, we also found that apoptotic cell death of retinal ganglion cells was induced in rat eyes by intravitreal administration of purified anti-NSE antibody. CONCLUSION: As suggested by previous reports, autoimmune response is one of the mechanisms related to glaucoma etiology and NSE may have an important function as an autoantigen.

Animals↗

Increased frequency of interleukin 4 producing CD4+ and CD8+ cells in peripheral blood from patients with systemic sclerosis.

OBJECTIVE: To-determine the relationship between the frequency of cytokine producing cells and systemic sclerosis (SSc), we examined the frequencies of interleukin 4 (IL-4) or IL-2 producing CD4+ or CD8+ T cells in peripheral blood mononuclear cells (PBMC) from patients with SSc. METHODS: PBMC from 23 SSc patients and 14 healthy controls were isolated from heparinized blood by density centrifugation. Purified PBMC were stimulated with immobilized anti-CD3 monoclonal antibody for 6 h in the presence of monensin. Cells were fixed, made permeable, and stained for intracellular cytokines in combination with staining for T cell surface markers, CD4, and CD8. RESULTS: The frequency of CD4+ T cells was negatively correlated with duration of SSc, whereas the frequency of CD8+ T cells was not correlated with duration. The frequencies of IL-4 producing (IL-4+) cells in CD4+ T cells and in CD8+ T cells from patients with SSc were both significantly higher than those from controls. In contrast, the frequencies of IL-2 producing (IL-2+) cells in CD4+ T cells and in CD8+ T cells from patients with SSc were both significantly lower than that from controls. Further, the ratios of IL-4+/IL-4+ + IL-2+ in CD4+ T cells and in CD8+ T cells were both negatively correlated with disease duration of SSc. CONCLUSION: These results suggest that type 2 cytokine producing T cells, not only CD4+ T cells but also CD8+ T cells, have important roles in the pathogenesis of SSc, especially in the early phase of SSc.

Aged↗

Retinal dysfunction in cancer-associated retinopathy is improved by Ca(2+) antagonist administration and dark adaptation.

PURPOSE: It was recently found that recoverin acts as an autoantigen recognized by sera of patients with cancer-associated retinopathy (CAR), and that CAR-like retinal dysfunction is produced by intravitreous administration of anti-recoverin antibody in Lewis rat eyes. To examine the pathologic molecular mechanism of CAR, and to elucidate an effective therapy for CAR, the function and morphology of CAR were compared with those of phototoxic retinal damage, another form of photoreceptor dysfunction, and the effect of nilvadipine, a Ca(2+) antagonist, on the retinal degenerations was studied, using these models. METHODS: Under different illumination conditions and/or medication with nilvadipine, the functional and morphologic properties of the retinas were evaluated after intravitreous injection of anti-recoverin antibody into Lewis rat eyes (six rats, 12 eyes in each experimental condition), using electroretinogram (ERG), rhodopsin phosphorylation, and light microscopy. RESULTS: Anti-recoverin antibody administered into the vitreous of Lewis rat eyes induced a significant decrease and increase of ERG responses and rhodopsin phosphorylation levels, respectively, under cyclic or continuous light. Similar changes were observed in eyes of rats bred under continuous illumination that did not receive anti-recoverin antibodies. However, anti-recoverin antibody-induced retinal dysfunctions were not observed in rat eyes under dark conditions. Administration of nilvadipine, a Ca(2+) antagonist, to the anti-recoverin antibody-treated rats and rats with phototoxic retinal dysfunction caused significant improvement of the deterioration of ERG and normalization of rhodopsin phosphorylation. CONCLUSIONS: The present data indicate that anti-recoverin antibody-induced retinal dysfunction was functionally similar to phototoxic retinal dysfunction and was markedly suppressed under dark conditions or by systemic administration of a Ca(2+) antagonist.

Animals↗

[A patient with recurrent breast cancer whose liver metastasis regressed following combined use of weekly docetaxel and MPA.5'-DFUR].

A 28-year-old woman who was 10 months pregnant was diagnosed with left breast cancer. She received preoperative chemotherapy and underwent mastectomy after parturition. Endocrine therapy and adjuvant CMF and CAF was administered, but a bone metastasis appeared 2 years later and a liver metastasis 3 years later. Weekly docetaxel and MPA plus 5'-DFUR combination therapy were successively and simultaneously administered. The liver tumor regressed, and the survival time was prolonged by 1 year and 6 months. This case suggests that the combined use of both therapies was safe for the patient in serious bad condition and had a strong antitumor effect.

Adult↗

[Morphometric analysis of retinal vascular endothelial cells in rats].

INTRODUCTION: In the present study, we observed the transformation of endothelial cells in the retinal vessel of normal rats and examined the relationship between morphometrical parameters and vessel calibers. MATERIALS AND METHODS: Retinal vessels of male Wistar-Kyoto rats were stained with an en face silver staining method and the vessel caliber, the axis of the cell oriented parallel to the longitudinal axis and to the transverse plane of the vessel, and the deviation angle of endothelial cells against the vessel axis were measured under a light microscope. RESULTS: As the vessel caliber increased, endothelial cells showed a tendency to extend along the longitudinal axis in the arterioles, but endothelial cells remained unchanged in the venules. The deviation angle of endothelial cells was nearly parallel to the vessel axis especially in the arterioles. CONCLUSIONS: Change in shape of endothelial cells in the retinal arterioles suggested a high shear stress in the large arterioles, and lower shear stress in the smaller arterioles with its decrease of caliber. In the venules, however, the cell shape was unchanged, and this suggests that the blood flow is fairly steady.

Animals↗

[Epidemiologic study of diabetic retinopathy in nine hospitals in the Aomori area].

PURPOSE: To examine the prevalence of diabetic retinopathy and the relationship between diabetic retinopathy and systemic risk factors. METHODS: A cross sectional study of diabetic retinopathy was conducted on 1,826 eyes of 913 randomly selected patients with type 2 diabetes in 9 central hospitals in Aomori Prefecture and the surrounding district. Retinopathy levels and maculopathy were assessed by binocular funduscopy, fundus photography and, if necessary, by fluorescein angiography. Multiple logistic regression analysis was performed to determine independent effects of systemic risk factors on diabetic retinopathy. RESULTS: The prevalence of background retinopathy was 31%, of preproliferative retinopathy 5%, and of proliferative retinopathy 5% in all patients. However, in 3 hospitals in which the patients were routinely examined by fluorescein angiography, background retinopathy was found to be present in 60%, preproliferative retinopathy in 5%, and prolifertive retinopathy in 7%. Maculopathy was found in 8% of diabetic patients and the prevalence was 11% in the eyes with background retinopathy, 40% with preproliferative retinopathy, and 50% with proliferative retinopathy. Multiple logistic regression analysis showed that retinopathy was significantly associated with duration of diabetes, methods of diabetic control, hypertension, nephropathy, and neuropathy. CONCLUSION: The detection rate of background diabetic retinopathy by fluorescein angiography was twice as sensitive as that by binocular funduscopy and fundus photography. The prevalence of maculopathy increases with the progression of retinopathy. Several systemic risk factors have significant association with diabetic retinopathy and maculopathy.

Aged↗

[Urachal xanthogranuloma caused by a swallowed fish bone: a case report].

A 30-year-old man was referred to our department with a complaint of bladder irritability and with development of high fever. Physical examination revealed a tender mass in the suprapubic area. Computed tomographic scan and magnetic resonance imaging indicated a cystic mass above the bladder dome, extending toward the umbilicus. Urachal abscess was suspected and the mass was excised en bloc with the urachus. The wall of the mass was thickened, and a linear foreign body was detected in the mass, which was considered to be a fish bone. Pathological diagnosis of the mass was xanthogranuloma. We speculated that a swallowed fish bone had penetrated the bowel and might have migrated into the urachal cyst, which induced a xanthogranulomatous change of the wall.

Adult↗

DNAinsight: a web based image processing system for large scale RLGS analysis.

DNA methylation occurring within the context of CpG site in the promoter element generally correlates with transcriptional silencing, delayed replication, condensed chromatin and mammalian genome imprinting (Nature Genet 24:101-2, 2000). We have been focusing attention on Restriction Landmark Genomic Scanning (RLGS) method as the powerful experimental procedure which can used to determine DNA methylation status change occurring on a genome simultaneously. To support systematic analysis with RLGS method, we have developed the automated processing algorithms for two-dimensional electrophoretograms of genomic DNA based on RLGS method (RLGS profile). Our powerful processing algorithms realize the automated spot recognition from RLGS profiles and the automated comparison of a huge number of such profiles. To make systematic RLGS analysis more easy and objective, we equipped our automated RLGS image processing algorithms with a WWW interface and relational database which stores the RLGS profile images together with their accompanying information, such as DNA sample specification, two-dimensional electrophoresis conditions and so forth. The web based RLGS image processing system "DNAinsight" can be accessed via URL http://www.methylome.jp/DNAinsight/.

Algorithms↗

Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study.

BACKGROUND: Ventricular arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot are devastating complications in adult survivors of early surgery, but their prediction remains difficult. METHODS: We examined surgical, electrocardiographic, and late haemodynamic data, and their relation to clinical arrhythmia and sudden death occurring over 10 years, in a multicentre cohort of patients with repaired tetralogy, who were alive in 1985. RESULTS: Of 793 patients (mean age at repair 8.2 years [SD 8], mean time from repair 21.1 years [8.7]) who entered the study, 33 patients developed sustained monomorphic ventricular tachycardia, 16 died suddenly, and 29 had new-onset sustained atrial flutter or fibrillation. Electrocardiographic markers (QRS duration, QRS rate of change between 1985 and 1995) were significantly greater in the ventricular tachycardia and sudden-death groups. Older age at repair was associated with a higher risk of sudden death and atrial tachyarrhythmia. Pulmonary regurgitation was the main underlying haemodynamic lesion for patients with ventricular tachycardia and sudden death, whereas tricuspid regurgitation was for those with atrial flutter/fibrillation. Despite adverse haemodynamics, no patient who died suddenly had undergone late reoperation. CONCLUSION: Arrhythmia and sudden death are important late sequelae for patients after repair of tetralogy of Fallot. The electrophysiological and haemodynamic substrate of sudden death resembled that of sustained ventricular tachycardia, with pulmonary regurgitation being the predominant haemodynamic lesion. Preservation or restoration of pulmonary valve function may thus reduce the risk of sudden death. Furthermore, electrocardiographic markers can help to identify patients at risk.

Adult↗