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Biomedical subjects

M Okano

Publications and source records attributed to M Okano.

At least 217 records · Page 12Linked to original sources

Adenovirus infection in patients with Kawasaki disease.

Two outbreaks of Kawasaki disease at different times and areas (Kyoto in 1982 and Sapporo in 1985) of Japan were studied retrospectively for the presence of antibodies to adenoviruses and herpesviruses. Only 2 of 12 (16.7%) consecutive acute phase sera of patients from the outbreak in 1982 and 1 of 10 (10.0%) sera from 1985 showed positive antibodies for the common adenovirus antigen by a complement fixation (CF) test, whereas 10 of 16 (62.5%) age- and sex-matched controls during the outbreak of Kawasaki disease in 1985 were seropositive by the CF test. In contrast, using a recently developed enzyme-linked immunosorbent assay (ELISA), 9 patients (75.0%) in 1982 and 9 patients (90.0%) in 1985 had antibodies to adenovirus type 2. In addition, 5 of 10 (50.0%) of the 1982 and 6 of 9 (66.7%) of the 1985 patients who were seronegative for CF antibodies were positive for IgM antibodies to adenovirus type 2. Fifteen (93.8%) controls were positive for antibodies to adenovirus type 2 by ELISA and only two sera showed negative CF antibodies with positive IgM antibodies to adenovirus type 2. Sequential sera from 4 patients in 1985 had either IgM or IgG antibodies by ELISA and eventually three became seropositive by the CF test in time. Additionally, no significant difference was noted with antibody status to herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) between patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenovirus Infections, Human↗

Immunovirological studies of fatal infectious mononucleosis in a patient with X-linked lymphoproliferative syndrome treated with intravenous immunoglobulin and interferon-alpha.

We have studied a 19-year-old male with X-linked lymphoproliferative syndrome (XLP) and infectious mononucleosis (IM) who was treated with high-dose immunoglobulin (500 mg/kg/day) and recombinant interferon (IFN)-alpha (2 x 10(6) IU/m2/day). Fulminant hepatitis was delayed; however, virus-associated hemophagocytic syndrome, cholestatic jaundice, and renal failure occurred terminally. Initially, nonspecific natural killer (NK) cell activity against K562 cells was normal but it gradually decreased. Although reactive T cells were markedly increased in his blood during the acute phase, spontaneous EBV-positive cell lines were easily established. Additionally, his mononuclear cells produced IFN-gamma but not IFN-alpha prior to treatment. Based on results of in vitro studies, we conclude that both IFN-alpha and IFN-gamma production are likely necessary for inhibiting EBV immortalization in vitro. Both IFN-alpha and -gamma were produced in cultures of B95-8 EBV-infected mononuclear cells from EBV-seropositive healthy individuals. These results suggest that defective EBV-specific cytotoxic T cell activity accompanied with defective or discordant IFN-alpha and -gamma production permitted the development of fatal IM in this patient. Combined treatment with immunoglobulin and IFN-alpha appeared to be partially effective during the early stage of this disease.

Adult↗

Severe chronic active Epstein-Barr virus infection syndrome and adenovirus type-2 infection.

Four patients from 4 to 24 years of age (3 males, 1 female) with generalized lymphadenopathy, hepatosplenomegaly, and intermittent fever associated with chronic active Epstein-Barr virus (EBV) infection were investigated. Laboratory data showed polyclonal gammopathy and a tendency for bone marrow suppression. Noteworthy were the extremely elevated immunoglobulin G (IgG) antibody titers to Epstein-Barr viral capsid antigen (VCA) (range, 10,240-81,920) and early antigen (EA) (range, 1,280-40,960). All patients had IgA antibodies to VCA and EA. Subtle, heterogeneous immune functional defects were observed in all four patients. Another unusual feature was our inability to establish spontaneous or B95-8 EBV-immortalized lymphoblastoid cell lines (LCLs) due to a marked cytopathic effect (CPE). Thus, we investigated for other viruses. Both IgG and IgM antibodies to adenovirus type-2 (Ad-2) were positive by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) test, suggesting recent or activated Ad-2 infection had occurred. Dual active EBV and Ad-2 infections were likely etiologic in this severe chronic active EBV infection syndrome.

Adenoviridae Infections↗

The effects of augmented hemodynamic forces on the progression and topography of atherosclerotic plaques.

In order to clarify mechanisms determining different degrees of vulnerability of atherogenesis between the apical and the proximal lateral walls at branchings, both regions of the inferior mesenteric artery in human autopsy cases were investigated electron microscopically. The lateral wall and the apex have been accepted by many researchers as the most preferential and the most resistant sites, respectively, for the disease. In regard to blood flow, the apex is exposed to laminar high shear stress, but the outer lateral wall to turbulent low shear stress. In newborns, intimal thickness in the apex was greater than that in the lateral wall, due mainly to the proliferation of SMC. After the 3rd decade, collagen fibers drastically increased in the apical intima, and SMC embedded between the collagen fibers, modulating their phenotypes from synthetic to contractile. In the lateral intima, SMC remained as the synthetic type. Synthetic SMC are considered capable of proliferation in the arterial wall. The lateral intima was generally abundant in proteoglycans and lacked collagen (including subendothelial basement membranes) as well as elastic fibers, particularly in the upper part of the intima. Such a structural difference may cause favorable conditions for atherosclerosis. Results of in vitro studies revealed that collagen gel suppressed proliferation of SMC and changed their phenotype from synthetic to contractile. Therefore, laminar high shear stress gives the arterial wall resistancy to atherogenesis through this phenotypic change. Rabbits showed preferential regions in certain areas of the flow divider for lipid deposition which were different from those of human beings. These regions were covered by ellipsoidal endothelial cells, which should be exposed to relatively low mean shear stress. Ellipsoidal endothelial cells had already been observed in intact rabbits. Therefore, we can conclude that atherogenic processes could be initiated by relatively low mean shear stress in either humans or rabbits.

Adolescent↗

Immune deficiency as a risk factor in Epstein-Barr virus-induced malignant diseases.

Epstein-Barr virus (EBV) is a ubiquitous DNA virus that normally infects silently, establishing lifelong latency. Substantial empirical observations support the view that immunodeficiency is permissive in EBV-induced lymphoproliferative diseases (LPD). Primary immune deficient patients such as those with X-linked lymphoproliferative disease and individuals with acquired immune deficiency secondary to immunosuppressive drugs for organ transplantation or individuals infected with human immunodeficiency virus are also at very high risk for lethal LPD. The importance of immunodeficiency and EBV in the development of head and neck carcinomas and uterine cervical carcinoma is less clear. Methods are available for detecting immunodeficiency and EBV genome and thus preventive strategies are being developed to preclude LPD from occurring.

B-Lymphocytes↗

[The histological expression of prostate-specific antigen and its clinical significance in patients with prostate cancer].

A total of 58 cases with prostatic diseases including benign hypertrophy (BPH) (n = 10) and adenocarcinoma (n = 48) were studied as to prostate-specific antigen (PA) with indirect enzyme immunohistochemistry. The expression of PA in the prostate, as well as the localization of PA in the tissue, was also studied in regard to cell differentiations, clinical stages, serum PA levels, with or without endocrine therapy, and prognosis of prostate cancer. Strong staining of PA was noted in epithelial cells of the gland, particularly on the ductal cavity, except for patients in the poorly differentiated carcinoma group. The overall positive rate for expression of PA was 100% in BPH and 73% (35/48) in prostate cancer. When prostate cancer was classified by cell differentiation, the positive rate was 100% (17/17) in the patients with well, 83% (10/12) moderately, and 42% (8/19) poorly differentiated carcinoma. When divided by clinical stages, the positive rate was 100% (1/1 and 9/9) in stages A and B each, 69% (9/13) in stage C, and 65% (17/26) in stage D. Of 33 cases whose serum PA values were determined, the histochemistry was positive in 67% of 12 patients with normal serum PA levels and in 86% of 21 in the elevated group. The prior to endocrine therapy group showed the presence of PA in 22 of 27 cases (82%) and a positive rate of 62% (13/21) was observed in the group during the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗

Pemphigus vulgaris associated with pregnancy. A case report from Japan.

We present a case of pemphigus vulgaris which developed during pregnancy. The newborn infant was normal. Bullous lesions were successfully treated by pulse therapy with high-dose corticosteroids. This is, to our knowledge, the first report in English from Japan describing pemphigus vulgaris associated with pregnancy.

Adult↗

Characterization of Epstein-Barr virus-induced lymphoproliferation derived from human peripheral blood mononuclear cells transferred to severe combined immunodeficient mice.

Mice with severe combined immunodeficiency (SCID) received 6 X 10(7) fresh human peripheral blood mononuclear cells (PBMC) intraperitoneally from Epstein-Barr virus (EBV)-seropositive and -seronegative donors. B95-8 EBV was inoculated intraperitoneally and intravenously to the mice 6 weeks after transfer of seronegative PBMC. Three of four mice transferred with PBMC from two EBV-seropositive donors and two of four mice from two EBV-seronegative donors inoculated with EBV developed fatal EBV-induced lymphoproliferative disease within 6 to 10 weeks. These tumors were oligoclonal or polyclonal by cytoplasmic immunoglobulin expression. Furthermore no consistent clonal chromosomal abnormalities were shown. Cell lines established from these tumors showed low cloning efficiency in soft agarose. In addition, latent membrane protein, B-lymphocyte activation antigen (CD23), and cell-adhesion molecules (ICAM-1, CD18) all were expressed in the EBV-positive infiltrating lymphoproliferative lesions in each mouse. These results suggest that lymphoid tumors are comparable to lymphoblastoid cell lines immortalized by EBV and are not malignant lymphomas such as Burkitt's lymphoma. This model may be useful for investigating mechanisms responsible for the growing numbers of lymphoproliferative diseases that are occurring in patients with inherited or acquired immunodeficiencies.

Animals↗

Anomalous posterior insertion of medial rectus muscle simulating congenital oculomotor palsy.

An unusual case was examined in our Hospital showing severe exotropia with adduction palsy. However, during surgery, anomalous posterior insertion of the medial rectus muscle was found, and the Hummelsheim operation was performed to correct the exotropia. To the best of the authors' knowledge, this is the first report of anomalous posterior insertion of the medial rectus muscle as a cause for congenital exotropia with adduction palsy.

Child↗

[Diagnosis of left ventricular aneurysm by exercise thallium-201 myocardial single photon emission computed tomography].

To diagnose and characterize post-infarction left ventricular aneurysms, we performed exercise thallium-201 myocardial single photon emission computed tomography (SPECT) combined with selective coronary angiography and left ventriculography. The subjects consisted of 79 patients with acute myocardial infarction; 42 with anteroseptal, three with both anterior and inferior, 29 with inferior and five with posterior infarction. Visual classification of ventricular wall morphology by either a horizontal or a vertical long-axis image was designed into convergent (C), parallel (P) and divergent (D) types, according to the interrelationship between either septal and lateral wall or anterior and inferior wall, respectively. This method was applied in post-stress and delayed images, and these patients were divided into five groups (Group A-E) in accordance with varying morphological types from the post-stress to the delayed as follows: C-C (Group A, 36 patients), P-C (Group B, 8), P-P (Group C, 7), D-P (Group D, 5) and D-D (Group E, 23). A high incidence (21/23) of a left ventricular aneurysm by left ventriculography was recognized in Group E patients in comparison with other Groups. Provided that either Group D or E (all patients had anterior infarction) had left ventricular aneurysms, the diagnostic sensitivity, specificity and accuracy were 89%, 92% and 86%, respectively. Two of three patients with false negative diagnosis had only apical involvement. Furthermore, these two Groups had significantly larger defect scores as calculated by polar maps than did the other three Groups. When patients with anterior infarction with defect scores of 200 or greater were defined positive, the sensitivity, specificity and accuracy of ventricular aneurysms were 96%, 75% and 86%, respectively. One false negative case was apical infarction, and one of the two false positive cases were extensive anteroseptal infarction involving the apex. These results suggest that a left ventricular aneurysm which is important in predicting prognostic sequence could be diagnosed only by exercise SPECT, and that it could be characterized by extensive and severe apicoanterior infarction and a divergent-type ventricular wall arrangement on a post-stress SPECT image.

Exercise Test↗

[Ataxia telangiectasia and characterization of its immunological disorders].

Ataxia telangiectasia (AT) is a primary immunodeficiency syndrome characterized by cerebellar ataxia, extrapyramidal signs, oculocutaneous telangiectasia, recurrent respiratory infections and development of malignancies. AT is a complex autosomal recessive disorder involving several systems other than lymphoid cells or the central nervous system. Such a diversity of abnormalities includes hypersensitivity of fibroblasts and lymphocytes to ionizing radiation (anomaly of DNA repair), non-random chromosomal rearrangements in lymphocytes, elevated serum level of alpha-fetoprotein, premature aging and endocrine disorders. A DNA processing or repair protein is the suspected common denominator in this pathology. Whatever the putative common underlying mechanism, AT patients have profound alterations of the humoral and cellular immune system whose mechanisms should be discussed in terms similar to those for other immunodeficiency diseases. The usual immunological abnormalities in this disease include decreased levels of CD 3 and CD 4 positive T lymphocytes, impaired delayed hypersensitivity, hypoplasia of thymus, decreased blast transformation in vitro in response to mitogen or antigenic stimulation, and decreased levels of serum IgA, IgE, and IgG 2 subclass. In this paper, the results of our recent studies on the defects of B cells in patients with AT were presented. (1) We found that the geometric means of IgA production in the supernatants of the lymphoblastoid cell lines established by EB virus, from all patients with AT, were significantly lower than those from healthy controls (P less than 0.01). (2) IgG subclasses of the patients' sera were also measured by ELISA, and IgG 4 was defective in four cases among six patients with AT.(ABSTRACT TRUNCATED AT 250 WORDS)

Ataxia Telangiectasia↗

[Measurement of incomitance patterns of vertical deviation in superior oblique palsy with a synoptometer].

By using a synoptometer we tried to compare the incomitance pattern of the vertical deviation in congenital superior oblique palsy with that of the vertical deviation in acquired superior oblique palsy. The data were transformed to a three-dimensional format by a computer to classify the incomitance pattern. With this method we found a difference in the incomitance pattern between congenital and acquired superior oblique palsy. In cases of congenital superior oblique palsy the vertical deviation increased proportionately with the change of gaze from abduction to adduction, since the incomitance caused by the horizontal change of gaze was more marked than that of the vertical change of gaze. However in cases of acquired superior oblique palsy the vertical deviation increased proportionately with change of gaze from up- to downward positions, therefore the incomitance caused by vertical change of gaze was more marked than that of the horizontal change of gaze. Moreover congenital superior oblique palsy was classified into three types according to the classification of Wieser and their incomitance patterns of vertical deviation were compared with each other.

Adolescent↗

[Surgical effect on incomitance of vertical deviation in superior oblique palsy measured by a synoptometer].

Using a synoptometer we evaluated the surgical effect on the incomitance of the vertical deviation in 26 patients with congenital superior oblique palsy. Either an inferior oblique recession or a superior oblique plication was performed. The two operative procedures reduced the incomitance caused by horizontal change of gaze, but produced incomitance by the vertical change of gaze and the incomitance increased proportionately with change of gaze from down to upward positions, which was not recognized preoperatively. As a result, the hyperdeviation was markedly reduced in the field of action of the overacting inferior oblique muscle. Moreover the surgical effect on the incomitance of the vertical deviation was studied in 13 patients with acquired superior oblique palsy treated with superior oblique plication. This procedure increased not only the incomitance in the upward positions by horizontal change of gaze, but also produced incomitance in adductive positions by vertical change of gaze. Therefore the hyperdeviation of the paretic eye was remarkably overcorrected in the field of action of the antagonist of the paretic superior oblique muscle.

Adolescent↗

Interferon-gamma in a family with X-linked lymphoproliferative syndrome with acute Epstein-Barr virus infection.

A 20-month-old male with fulminant infectious mononucleosis and the X-linked lymphoproliferative syndrome (XLP) was studied. Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA) and EBV DNA were detected in various tissues. Despite a combined treatment with acyclovir, immunoglobulin, and methylprednisolone, the patient deteriorated rapidly. Following treatment with recombinant interferon-gamma (IFN-gamma), defervescence occurred and circulating EBNA-positive cells markedly decreased. IFN-gamma prior to treatment ranged from 10.8 to 24.5 U/ml in the patient's serum and increased linearly post exogenous IFN-gamma treatment. His natural killer (NK)-cell activity remained in the normal range throughout his illness but autologous EBV-infected cells were not killed in vitro by his peripheral blood lymphocytes (PBL). These results suggest that patients with the fatal infectious mononucleosis phenotype of XLP may produce endogenous IFN-gamma. Defective cytotoxic T cells against EBV-infected cells seem to be responsible for the fulminant infectious mononucleosis in this patient.

Acute Disease↗

Enzyme-linked immunosorbent assay (ELISA) for detecting antibodies in sera of patients with adenovirus infection.

The 41 distinct antigenic types of adenoviruses (Ads) are responsible for a broad spectrum of diseases in humans. We have developed an enzyme-linked immunosorbent assay (ELISA) using adenovirus (Ad) infected MRC-5 cells for detecting IgG and IgM antibodies to Ads. Using the ELISA, we detected IgG antibodies in 100% (20/20) of sera from normal adults (geometric mean titer, GMT = 1840.8, range = 40-20,480) and IgM antibodies in 3 of 20 sera (15%) with a GMT of 25.1. Our indirect immunofluorescence (IF) technique also detected IgG antibodies in 100% of these sera (GMT = 248.3, range = 40-5,120) and IgM antibodies in the 3 samples reactive in ELISA (GMT = 20.0, range = less than 5-40). In contrast, the complement fixation (CF) test detected antibodies to Ads in only 65% (13/20) of these sera (GMT = 10.9, range = less than 4-32). Moreover, IgG and IgM responses could not be distinguished using CF. Thus the sensitivity of these three techniques is greatest for ELISA. Additionally, a study of sequential sera from 3 patients with acute Ad infection disclosed seroconversion using all three methods. Both the ELISA and IF techniques permit the detection of transition from IgM to IgG, whereas CF only detects conversion from seronegativity to seropositivity. Finally, preliminary data suggest that the IgM response as measured by ELISA is specific for subgroups or types of Ad. This newly devised ELISA may be useful for detecting Ad infections.

Adenoviridae Infections↗