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Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 181 records · Page 10Linked to original sources

Association of an insertion polymorphism of angiotensin-converting enzyme gene with the activity of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) shows various clinical manifestations, which are characterized by inflammation in many different organ systems. The cause of SLE is still unclear; however, the immunological abnormalities are considered to be responsible for the pathogenesis of SLE. As angiotensin I-converting enzyme (ACE) has been reported to be associated with various immunological phenomena, we investigated the correlation between insertion (I)/deletion (D) polymorphism of the ACE gene and the disease activity of SLE. Ninety-three patients with newly diagnosed SLE were enrolled in this study. ACE genotype was determined by the polymerase chain reaction (PCR). We measured serum levels of anti-double-stranded (ds) DNA antibody (Ab) and serum levels of total complements (CH50) as the parameter for lupus activity. Moreover, we evaluated the clinical disease activity by calculating SLE disease activity index (SLEDAI). Individuals with II genotype showed a significant increase in SLE activity. Patients with the ACE II genotype showed a higher serum level of anti-dsDNA Ab (14.3 IU/ml (5.475, 74.6, median (25th centile, 75th centile)) than those with the DD genotype (4.65IU/ml (4.05, 6.8)) (P<0.01). Moreover, patients with the 11 genotype also showed lower levels of serum CH50 than those with the DD genotype (P < 0.01). Patients with the II1 or DI genotype had significantly higher SLEDAI score than those with the DD genotype (P < 0.01). These results suggest that the ACE genotype could be associated with the disease activity of SLE. ACE insertion polymorphism might be used as one of predictive factors for the activity of lupus.

Adult↗

Evaluation of propolis (II): effects of Brazilian and Chinese propolis on histamine release from rat peritoneal mast cells induced by compound 48/80 and concanavalin A.

To establish a biological method for evaluating propolis and to reveal their anti-allergic action, the effects of the ethanol and water extracts (EA-ET and WA-WT, respectively) from Brazilian, Chinese and Japanese propolis on the histamine release induced by compound 48/80 and concanavalin A (Con A) were investigated. The relation between the inhibitory activities of these extracts on the histamine release and their E(1 cm)1% values were also examined. As a result, the following was found: 1) 0.003-0.01% ethanol and 0.03-0.1% water extracts inhibited the histamine release induced by compound 48/80 and Con A, and the inhibitory potencies of the former extracts were more than 10 times stronger than those of the latter extracts, making it clear that both the ethanol and water extracts possess an anti-allergic action; 2) most of the ethanol and water extracts responded to the histamine release induced by both the histamine releasers in a concentration-dependent manner; 3) the inhibitory activities of 0.003% EM from Hebei Province, EP from Sichuan Province, EQ from Zhejiang Province and ER from Anhui Province in China were weaker than those of 0.01% corresponding extracts, whereas 0.001% ED-EH from Brazilian propolis, EM, EN from Henan Province in China and EP-ER promoted the Con A-induced histamine release of more than 10%, suggesting that such extracts must be carefully given to humans; 4) the inhibitory potencies of only 0.03-0.1% water extracts from Chinese propolis on the Con A-induced histamine release related excellently with their E(1 cm)1% values; 5) from the results of the relation between the inhibitory potencies of the propolis extracts and their E(1 cm)1% values, it was suggested that an unknown compound, being a poorly water-soluble compound which is a non-flavonoid, with an anti-allergic action is contained in propolis; 6) to precisely evaluate the anti-allergic action of the propolis, the biological method, which measures the inhibitory activities of the propolis extracts on histamine release, was markedly superior to the physicochemical method.

Animals↗

Use of new magnetic attachments for implant-supported overdentures.

A newly designed magnetic attachment system for external hexed implants with a standard abutment platform has been developed. This system has certain definite advantages over bar attachments and ball attachments, which are frequently utilized for implant-supported overdentures. Especially, it can be applied to cases with reduced vertical dimension of occlusion because the total height of the magnet and the keeper is only 2.3 mm when assembled. In addition, detrimental lateral stresses to the fixture are greatly alleviated due to very low attractive forces horizontally. Favorable clinical results using this new magnetic attachment system have been obtained, and it may be considered a useful addition to overdenture therapy using any external hexel implant with a standard abutment platform, such as the Brånemark implant system.

Aged↗

[Relationship between cognitive function and discharge place among stroke patients after rehabilitation].

One hundred and ninety-nine elderly stroke patients, who received rehabilitation treatment, were examined, to clarify the relationship between cognitive function and discharge place. The patients who moved to long-term care facilities showed more severe disabilities of basic activities of daily living (ADL), more frequent incontinence, and lower functional impairments (Brunnstrom stage), compared with those discharged to their home. Multivariate regression analysis was done with discharge place as the dependent variable. Independent variables were age, sex, kind of stroke, rehabilitation period, level of ADL and IQ on Kohs test, or performance IQ on the Wechsler Adult Intelligence Scale. Older age, higher levels of ADLs, and higher scores on Kohs test IQ or Wechsler Adult Intelligence Scale Performance IQ were all significantly linked with home discharge. These results suggest that non-verbal cognitive dysfunction may affect discharge place in elderly stroke patients after rehabilitation therapy.

Activities of Daily Living↗

Langerhans cells in the human oviduct mucosa.

Langerhans cells (LCs) are the predominant antigen-presenting cells in epithelial tissues. They have been known to be present in the vagina and uterine cervix. In the present study, localization of LCs in the oviduct was investigated by electron microscopy and immunohistochemistry using an anti-CD1a (CD; cluster of differentiation) antibody. Although the cell density was variable, CD1a-positive LCs were detected in the oviduct epithelium. Their occurrence was most common in women at the age of 40 to 59. LCs extended cell processes along the base of the epithelium and were ultrastructurally characterized by rod-shaped Birbeck granules and a well-developed Golgi apparatus. LCs, together with lymphocytes and macrophages, are considered to engage in the mucosal immune system of the oviduct.

Adult↗

[Pilot study of relapsed osteosarcoma and brain tumor with ifosfamide, carboplatin and etoposide (ICE therapy)].

Ifosfamide, Carboplatin and Etoposide (ICE) therapy was used to treat 4 patients, 2 with refractory osteosarcoma, and one each with relapsed brain tumor and newly diagnosed brain tumor. ICE therapy was administered in doses of Ifosfamide 1,800 mg/m2 x 5, Carboplatin 400 mg/m2 x 2 and Etoposide 100 mg/m2 x 5. A total of 30 courses were administered. Two cases of osteosarcoma had a stable disease (range, 3-9 months) and 2 cases of brain tumor had a complete response by magnetic resonance imaging. Moderate or severe toxicity evaluated on a per course basis included: neutropenia 83%, thrombocytopenia 93%, fever 30%, hepatotoxicity 3%, and hemorrhagic cystitis 3%. The median time to hematologic recovery was 20 days. ICE therapy is highly effective for the treatment of refractory or recurrent solid tumors with acceptable toxicity.

Adolescent↗

[A case of Bartter's syndrome with chronic renal failure due to chronic interstitial nephritis].

We report a case of 45-year-old women with Bartter's syndrome and concomitant renal dysfunction. In 1986, the patient demonstrated muscle weakness and serum potassium levels as low as 1.1 mEq/l. She was suspected of having Bartter's syndrome because of hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normotension. Pretibial edema developed in 1989 for which she received 40 to 100 mg/week of furosemide intermittently for the next 5 years. Her serum potassium level ranged from 1.5 to 3.9 mEq/l. In 1991, her serum creatinine level rose to 2.1 mg/dl, then continued to increase gradually. She was admitted to our hospital in 1994 for evaluation of the renal dysfunction. Decreased creatinine clearance (44 ml/min) and a defect in urinary concentrating capacity (Fishberg's test, 370 mOsm/kg.H2O) were detected. Renal biopsy revealed juxtaglomerular cell hyperplasia. These findings resulted in the diagnosis of Bartter's syndrome. The renal biopsy also showed diffuse interstitial fibrosis and marked tubular atrophy. We postulate in this case that long-term hypokalemia due to Bartter's syndrome and the administration of furosemide led to chronic interstitial nephritis and renal dysfunction.

Bartter Syndrome↗

[A case of polyangiitis overlap syndrome].

A 47 year old man was admitted to a local hospital because of fever and severe epigastric pain. Laboratory examination showed eosinophilia (9,812/microliter) and an elevated serum IgE level (934 IU/ml). Multiple hemorrhagic gastric ulcers and a left adrenal tumor was also found. The gastric ulcers were resistant to conservative therapy. On the eighth hospital day, total gastrectomy and left adrenalectomy were performed. Surgical specimens from the stomach and adrenal gland showed necrotizing angiitis with infiltration of eosinophils, and thrombus formation. Eosinophilia was persistant to the treatment by corticosteroid and immunosuppressant. Thereafter polymononeuropathy in lower limbs and necrotizing lesions in toes developed and were resistant to medication and gangrionic block. According to the clinical and pathological findings, we made diagnosis of this case as polyangiitis overlap syndrome with some features of Allergic granulomatous angiitis and Polyarteritis nodosa.

Churg-Strauss Syndrome↗

[Changes in QOL in patients with brain tumors measured by mood changes during and after treatment].

UNLABELLED: Patients with brain tumors are exposed to severe stress which may have an influence on their quality of life (QOL). To measure QOL in those patients, we measure their mood state during and after the treatments. MATERIALS: 16 patients who were admitted to our department for treatment of brain tumors, were included in the study. The tumors included 5 gliomas, 6 meningiomas and others. They were 7 males and 9 females, and age distributed from 19 to 74 years old. All patients presented more than 90% of the Karnofsky performance score (KPS) on discharge, so they were expected to return to their previous social life. METHOD: The self-answering tests were performed on admission (Pre), on discharge (Post 1), and at more than 5 months after the discharge (Post 2). The tests included an original questionnaire asking consent to admission and treatment, and concerning the feeling of disability to cope with conditions of living, Cornell Medical Index (CMI) which measured the neurosis, and Profile of mood state (POMS) which measured the 6 subscales of patients mood states including tension-anxiety (TA), depression (D), anger-hostility (AH), vigor (V), fatigue (F), and confusion (C). RESULTS: The questionnaire showed that the patients feel satisfied with having consented to the treatment. The feeling of disability to cope with living became stronger in Post 2 than in Pre. CMI showed a borderline of neurosis in three patients on admission, and in four patients in Post 2. Only the TA of POMS subscale improved significantly in Post 2. However, other subscales were unchanged. It is characteristic that all of the subscales of POMS showed less disturbance on discharge compared with that on admission, but, they returned to the Prelevel after they returned to social life. CONCLUSIONS: Patients with brain tumors have satisfactory consent to the treatment, however, they feel disability to cope with social life. On discharge, they showed a better mood state compared to that on admission, but the mood state turned for the worse again during the follow-up period. It is evident that patients with brain tumors are exposed to severe stress even after the completion of the treatment. The results necessitate our taking patients' mental health into consideration for our treatment protocol.

Adult↗

[Bone marrow relapse in high-risk pediatric patients with acute lymphoblastic leukemia: a comparison of relapse times and initial clinical features of patients on different protocols. Children's Cancer and Leukemia Study group (CCLSG)].

To clarify the efficacy of modern intensive chemotherapy for ALL patients with unfavorable features, we compared the time to failure and initial clinical features of children who relapsed in the bone marrow or combined sites, as documented by early CCLSG studies (H811 and H851; 1981-1987) and later studies (H874 and H/HH911; 1987-1993) concerning high-risk ALL patients. In the later studies patients outcomes with new intensive regimens employing early intensification and reinduction therapy were apparently better than those of patients in the early studies with conventional regimens. When we compared the number of relapsed patients based on duration of first remission, we found that the improved outcomes for patients in the later studies were due to a decrease in the number who relapsed 7-36 months after the start of treatment (intermediate relapse), and that the percentage of those who relapsed within the first 6 months of therapy (early relapse) was higher. Patients with high initial WBC counts tended to relapse much earlier than those with low initial WBC counts. However, in the later studies, patients with high WBC counts often relapsed after the termination of therapy (late relapse). These results suggest that the intensive chemotherapy regimens used in the later studies can prevent the development of drug resistant leukemic clones, except in extremely high-risk patients likely to relapse within the first 6 months of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Studies of childhood non-Hodgkin's lymphoma--treatment results with the CCLSG NHL 960 protocol. Children's Cancer and Leukemia Study Group (CCLSG)].

We report here on the preliminary treatment findings of a CCLSG NHL 960 study that was initiated in March 1996. In this study, 37 patients with non-Hodgkin's lymphoma were assigned to 4 different treatment groups according to disease stage and histology: (1) localized disease; (2) advanced disease, lymphoblastic type; (3) advanced disease, large cell type; and (4) advanced disease, Burkitt type. The first three groups received the modified protocols of the NHL 890 study. Groups 1 and 3 received COPADM induction therapy (CPM, VCR, PRD, ADR, and MTX). After achieving remission, Group 1 received only maintenance therapy consisting of alternate administration of 7 drugs, while Group 3 received additional intensification therapy with combination chemotherapy consisting of MTX and Ara-C, followed by a maintenance phase involving the administration of 9 drugs. Group 2 received COPADL induction therapy (CPM, VCR, PRD, ADR, and LASP) and consolidation/intensification therapies followed by a maintenance phase. Group 4 received short-term intensive COPADM polychemotherapy. Twelve patients with localized with localized disease (stage I-II) and 25 patients with advanced disease (stage III-IV) were enrolled in this study. Except for 2 patients in the advanced disease stages who died earlier in the course of the study, all patients remained in remission.

Adolescent↗

Afadin: A novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction.

A novel actin filament (F-actin)-binding protein with a molecular mass of approximately 205 kD (p205), which was concentrated at cadherin-based cell-to-cell adherens junction (AJ), was isolated and characterized. p205 was purified from rat brain and its cDNA was cloned from a rat brain cDNA library. p205 was a protein of 1,829 amino acids (aa) with a calculated molecular mass of 207,667 kD. p205 had one F-actin-binding domain at 1,631-1,829 aa residues and one PDZ domain at 1,016- 1,100 aa residues, a domain known to interact with transmembrane proteins. p205 was copurified from rat brain with another protein with a molecular mass of 190 kD (p190). p190 was a protein of 1,663 aa with a calculated molecular mass of 188,971 kD. p190 was a splicing variant of p205 having one PDZ domain at 1,009-1,093 aa residues but lacking the F-actin-binding domain. Homology search analysis revealed that the aa sequence of p190 showed 90% identity over the entire sequence with the product of the AF-6 gene, which was found to be fused to the ALL-1 gene, known to be involved in acute leukemia. p190 is likely to be a rat counterpart of human AF-6 protein. p205 bound along the sides of F-actin but hardly showed the F-actin-cross-linking activity. Northern and Western blot analyses showed that p205 was ubiquitously expressed in all the rat tissues examined, whereas p190 was specifically expressed in brain. Immunofluorescence and immunoelectron microscopic studies revealed that p205 was concentrated at cadherin-based cell-to-cell AJ of various tissues. We named p205 l-afadin (a large splicing variant of AF-6 protein localized at adherens junction) and p190 s-afadin (a small splicing variant of l-afadin). These results suggest that l-afadin serves as a linker of the actin cytoskeleton to the plasma membrane at cell-to-cell AJ.

Actins↗

Two-dimensional distribution of Gi2alpha in the plasma membrane: a critical evaluation by immunocytochemistry.

Caveolae have been postulated as a center for signal transduction, because many signaling molecules are concentrated in caveolin-rich fractions. We took Gi2alpha as an example and examined whether it is constitutively concentrated in caveolae. First, the behavior of caveolin and Gi2alpha in density-equilibrium ultracentrifugation was reexamined. By collecting fractions efficiently, caveolin and Gi2alpha were found to distribute differently. Secondly, by novel immunocytochemical methods it was found that the labeling density of Gi2alpha was 2.29 times higher in caveolae than in the non-caveolar plasma membrane. The results indicate that the concentration of Gi2alpha in caveolae is lower than deduced from most biochemical studies.

Caveolin 1↗

Detection of three transthyretin gene mutations in familial amyloidotic polyneuropathy by analysis of DNA extracted from formalin-fixed and paraffin-embedded tissues.

We identified three different missense mutations of the transthyretin (TTR) gene in three Japanese patients with familial amyloidotic polyneuropathy by analysis of their DNAs extracted from formalin-fixed and paraffin-embedded tissues. Patient 1 carried the TTR methionine-30 (Met) mutation (G to A transition at position 1679). DNA sequencing analysis of the TTR gene from patient 2 showed a G to T transversion at position 3830 in exon 3, resulting in an amino acid replacement of serine-50 (Ser) with isoleucine (Ile). Patient 3 had the novel mutation (G to T transversion at position 7314) in exon 4, resulting in an amino acid replacement of alanine-109 (Ala) with Ser. We established DNA diagnostic methods for detecting TTR Ile50 by polymerase chain reaction (PCR)-induced mutation restriction analysis and for TTR Ser109 by PCR-restriction fragment length polymorphism. Gene analysis of archival paraffin-embedded tissues is useful for the precise diagnosis of FAP and for clarifying its molecular pathogenesis in patients for whom fresh genomic DNA is not available.

Aged↗

Peculiar distribution of fodrin in fat-storing cells.

Fat-storing cells (FSCs) show unique morphology containing many lipid droplets in the cytoplasm. In this study, we found that a membrane skeletal protein, fodrin, shows peculiar distribution in FSCs of rat liver. By immunofluorescence microscopy of FSCs in culture, intense labeling for fodrin was seen as coarse filaments in the cytoplasm. Especially in FSCs isolated from vitamin A-treated rats, the labeling was often seen as many small rings in the cytoplasm. In contrast, labeling for fodrin in human fibroblasts or rat adipocytes in culture was seen diffusely in the cell cortex. Distribution of actin, tubulin, vimentin, and desmin in FSCs was also examined, but none of them appeared correlated with fodrin. By immunoelectron microscopy using nanogold labeling with silver enhancement, positive labeling for fodrin was seen around some lipid droplets in FSCs in vivo. We assume that the peculiar distribution of fodrin may be related to the morphological characteristics of FSCs.

Adipocytes↗

Kazuo Ogawa

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Journal Article↗

Streptococcal preparation OK-432 is a potent inducer of IL-12 and a T helper cell 1 dominant state.

Streptococcal preparation OK-432 is a bacterial immunopotentiator extensively used in Japan for adjuvant cancer therapy. Using a C57BL/6 mouse model, OK-432 was found to induce multiple cytokines including the Th1 polarizing cytokine IL-12. Expression of IL-12 protein by murine splenocytes was restricted to macrophages and B cells and led to high levels of IFN-gamma production from both CD4+ and CD8+ T cells. Of the Th2 cytokines IL-4 and IL-10, only IL-10 protein was detected and originated primarily from the adherent cell population. Its expression was delayed relative to IL-12. A similar pattern of cytokine induction was observed from human PBMCs. OK-432-driven IFN-gamma production was inhibited by anti-IL-12 Ab, anti-IL-2 Ab, anti-TNF-alpha Ab, and anti-IL-2R alpha Ab, suggesting that IFN-gamma production from Th1 cells is induced by the cooperation action of these cytokines through the IL-2R alpha pathway. When compared with another widely used immunopotentiator bacillus Calmette-Guérin (BCG), OK-432 was a stronger IL-12 and IFN-gamma inducer. Furthermore, the mechanism of IFN-gamma induction by OK-432 differed from BCG in that coincident granulocyte-macrophage CSF and IL-1 expression played little to no role. These results suggest that OK-432 is a potent multicytokine inducer, specifically a strong inducer of IL-12, and that OK-432 may exert its antitumor effect by promoting a Th1-dominant state.

Adjuvants, Immunologic↗