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T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 145 records · Page 8Linked to original sources

Development of a latex immunoturbidimetric assay for the automated measurement of alpha2 plasmin inhibitor-plasmin complex in human plasma.

We have developed a rapid, sensitive, and quantitative latex immunoturbidimetric assay for the measurement of alpha2 plasmin inhibitor-plasmin inhibitor complex (PIC) in human plasma. The method is based on the latex agglutination reaction using a suitable pair of monoclonal antibodies. One reacts with plasmin and the other reacts with alpha2 plasmin inhibitor. In this assay, we added 6-aminohexanoic acid to the reaction buffer in order to avoid the nonspecific latex agglutination caused by precursor proteins such as plasminogen. We used this method with an automatic analyzer HITACHI 7150 (Hitachi Ltd., Hitachi, Japan) and measured PIC within the range of 0.2 to about 50 mg/mL in only 15 minutes. The precision indices (CV%) of intra-assays and interassays were <4.4% and <3.4%, respectively. The influence of plasminogen or alpha2 plasmin inhibitor on plasma was negligible. Based on these results, it is considered that this method would be useful for evaluation of a broad spectrum of fibrinolytic disorders, particularly disseminated intravascular coagulation.

Aminocaproic Acid↗

Tyrosine-phosphorylated caveolin-1: immunolocalization and molecular characterization.

Caveolin-1 was discovered as a major substrate for v-Src, but the effect of its tyrosine phosphorylation has not been known. We generated a specific antibody (PY14) to caveolin-1 phosphorylated at tyrosine 14 and studied the significance of the modification. By Western blotting of lysates of v-Src-expressing cells, PY14 recognized not only a 22-kDa band (the position of nonphosphorylated caveolin-1) but bands at 23-24 and 25 kDa. Bands of slower mobility were diminished by dephosphorylation and were also observed for mutant caveolin-1 lacking tyrosine 14. By immunofluorescence microscopy, PY14 did not label normal cells but detected large dots in v-Src-expressing cells. Immunoelectron microscopy revealed that the dots corresponded to aggregated caveolae and/or vesicles of various sizes; besides, the label was observed in intramembrane particle-free areas in the plasma membrane, which appeared to have been formed by fusion of flattened caveolae. A positive reaction with PY14 was found in normal cells after vanadate or pervanadate treatment; it occurred mainly at 22 kDa by Western blotting and was not seen as large dots by immunofluorescence microscopy. Detergent solubility, oligomerization, and association with caveolin-2 were observed similarly for caveolin-1 in normal and v-Src-expressing cells. The results indicate that phosphorylation of caveolin-1 in v-Src-expressing cells occurs at multiple residues and induces flattening, aggregation, and fusion of caveolae and/or caveolae-derived vesicles.

Animals↗

Clinicopathological comparisons of familial and sporadic cases in 219 consecutive Japanese epithelial ovarian cancer patients.

BACKGROUND: It is estimated that approximately 5-10% of epithelial ovarian cancer patients in Western countries are associated with an autosomal dominant inheritance with variable penetrance. There are a few reports of familial ovarian cancer in Japan and considerable uncertainties remain regarding Japanese familial ovarian cancer. The aim of this study was to clarify the clinicopathological features of Japanese familial ovarian cancer. METHODS: We studied clinicopathological findings for 219 consecutive epithelial ovarian cancer patients treated at our institution from April 1987 to September 1997. RESULTS: Eleven patients in nine families were diagnosed as familial ovarian cancer and the incidence of familial cases was 5.0%. Most women (90.9%) with familial cases were diagnosed as the breast ovarian cancer syndrome, whereas ovarian cancer associated with hereditary nonpolyposis colorectal cancer was relatively rare (9.1%). Serous adenocarcinoma, high histological grade, advanced FIGO stage and breast cancer as multiple primary cancer were significantly more common in familial cases compared with sporadic cases (p < 0.001, p < 0.05, p < 0.005 and p < 0.005, respectively). Earlier age of onset was thought to be a characteristic of familial ovarian cancer in Western countries; however, we did not find any difference in age at diagnosis between familial and sporadic cases (53.4 vs 51.3 years). The prognosis of familial ovarian cancer remains controversial and our data did not show a significant difference (p = 0.45) in prognosis between these two groups. CONCLUSION: These findings, except for age at diagnosis, in Japanese familial ovarian cancer are in accordance with the features of familial ovarian cancer in Western countries.

Asian People↗

Magnetic resonance imaging findings in cerebral fat embolism: correlation with clinical manifestations.

OBJECTIVES: Cerebral fat embolism (CFE) is a serious complication after fracture of long bones. The mortality rate of CFE may be high. However, recent progress in treatment may decrease the mortality. We studied the validity of magnetic resonance imaging (MRI) to detect and grade severity of CFE in 11 patients with CFE. METHODS: Glasgow Coma Scale score, PaO2, PaCO2 at the onset, and minimal hemoglobin and platelet levels were monitored, and phagocytes in bronchoalveolar lavage fluid were counted. Brain computed tomographic and MRI scans were performed serially. MRI findings were graded into four categories according to the severity of T2-weighted images. RESULTS: High-intensity T2 signals were identified in the various brain regions as early as 4 hours after onset of CFE. The maximum MRI grade significantly correlated with Glasgow Coma Scale score at the onset of CFE (p < 0.01). High-intensity T2 signal lesions fused and enlarged with time. In most cases, they diminished within 2 weeks. Three patients had persistent morbidity. CONCLUSION: MRI-T2-weighted imaging seems to be the most sensitive imaging technique for diagnosing CFE, and correlates well with the clinical severity of brain Injury. With the aid of proper treatment for pulmonary fat embolism, CFE is a potentially reversible disease that can have a good outcome.

Adult↗

Diversity of leukaemic cell morphology in ATL correlates with prognostic factors, aberrant immunophenotype and defective HTLV-1 genotype.

To investigate the diversity of morphology in adult T-cell leukaemia/lymphoma (ATL) and its possible association with the pathophysiology of ATL, we selected 36 acute cases and 14 chronic cases phenotypically confirmed to have >90% ATL cells in peripheral blood mononuclear cells. Prototype ATL cells were observed in all cases, although the percentage of all lymphoid cells varied considerably (48.9 +/- 23.8 in acute type, 29.6 +/- 18.9 in chronic type; P = 0.015). Chronic lymphocytic leukaemia (CLL)-like morphology with round nuclei was more frequent in chronic type than in acute type (52.0 +/- 24.9% v 16.6 +/- 13.1%; P < 0.0001). Unusual morphology (UM; lymphoblastic, vacuolated, granular pleomorphic or large cells) was more frequent in acute type than in chronic type (20.1 +/- 18.7% v 2.7 +/- 3.2%; P < 0.0001). Furthermore, there were significant negative and positive correlations of % CLL-like cells and % UM cells respectively, with serum LDH level, hypercalcaemia, performance status, and total number of involved lesions. Cases with aberrant immunophenotype (n = 6) or defective HTLV-1 integration (n = 22) showed lower % CLL-like cells and higher % UM cells than other cases, respectively. Cases with >50% CLL-like cells (n = 7; all chronic type) were younger (53.1 +/- 12.2 v 66.9 +/- 10.6 years; P = 0.038) and showed longer acute-crisis free survival (mean: 16.7 v 3. 0 years; P = 0.012) than chronic cases with <50% CLL-like cells. These results suggest that diversity in genotype, phenotype, morphology and behaviour of ATL are closely associated, and that CLL-like morphology is a good prognostic factor for chronic type.

Adult↗

Gonadotropin-releasing hormone receptor mRNA expression in the ovaries of neonatal and adult rats.

Recent studies have shown that gonadotropin-releasing hormone (GnRH) can exert various effects on the rat ovary by acting through its specific receptors. To determine the cell types responsive to the action of GnRH under physiological conditions in the ovary, distribution of the GnRH receptor mRNA was studied histologically by in situ hybridization in neonatal and adult rats. Expression of the luteinizing hormone receptor mRNA was also examined to judge the growing state of follicles and the corpora lutea. In neonatal rat ovaries, no significant GnRH receptor mRNA signal was detected until 5 days after birth. The expression was first observed at 10 days in the interstitial cells. At 15 days of age, the receptor mRNA was expressed in the granulosa cells of most preantral and early antral follicles, while no hybridization signal was detected in oocyte and theca cells. In adult cycling rats, GnRH receptor mRNA was detected mainly in the granulosa cells of most follicles and luteal cells. The granulosa cells of atretic follicles showed a very high level of the mRNA expression throughout their degenerating process. A strong hybridization signal was also detected in the mural granulosa cells of mature follicles. Newly formed (developing) corpora lutea exhibited signals with moderate intensity in the luteal cells, and the older ones showed weaker signals. The finding that the initial expression of GnRH receptor mRNA was seen in the interstitial cells of neonatal ovaries implies an unknown function of the ovarian GnRH receptor in ovarian development. The high level expression of GnRH receptor mRNA in atretic and mature follicles supports the putative roles of GnRH in the induction of follicular atresia and ovulation in rat ovaries.

Animals↗

Changes in levels of phosphorus metabolites in temporal lobes of drug-naive schizophrenic patients.

OBJECTIVE: The authors examined phospholipids and high-energy phosphorus metabolism in the temporal lobes of drug-naive schizophrenic patients. METHOD: In vivo 31P magnetic resonance spectroscopy was performed on 17 first-episode, drug-naive schizophrenic patients and 17 age- and gender-matched healthy subjects. RESULTS: Patients showed higher levels of phosphodiesters and lower levels of phosphomonoesters than the comparison group. Phosphocreatine levels were increased in the left temporal lobes of patients. CONCLUSIONS: The results suggest disturbed membrane phospholipid metabolism in both temporal lobes and decreased energy demands in the left temporal lobes of drug-naive schizophrenic patients.

Adult↗

Relationship between the clinical efficacy of pentoxifylline treatment and elevation of serum T helper type 2 cytokine levels in patients with human T-lymphotropic virus type I-associated myelopathy.

OBJECT: Previously, we reported the efficacy of pentoxifylline (PTX) treatment in human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). Here, we clarify the relationship between the clinical efficacy of PTX treatment and elevation of T helper type 2 (Th2) cytokine levels in HAM patients. PATIENTS AND METHODS: PTX (300 mg) was administered daily by the oral route to 12 HAM patients for 4 weeks. We assessed the relationship between the changes in neurological status (motor disability scores, the degree of spasticity on neurological examination, and the time required to walk 10 m) and the changes in serum and cerebrospinal fluid (CSF) levels of interferon-gamma (IFN-gamma) as a Th1 cytokine and interleukin-4 and -10 (IL-4 and -10) as Th2 cytokines measured by an EASIA (enzyme-amplified sensitivity immunoassay) kit. RESULTS: PTX treatment induced incremental increases in the levels of IL-4 and IL-10 in both sera and CSF of 6 HAM patients. Clinical improvement was associated with this elevation in IL-4 and IL-10. PTX treatment also induced a decrease in IFN-gamma levels in the sera of 6 HAM patients, but this was not correlated with clinical improvement. CONCLUSION: These results suggest that the correction of the immunological imbalance in Th1 to Th2 cytokine responses, with upregulation of IL-4 and IL-10, may account for the clinical improvement in HAM patients treated with PTX.

Administration, Oral↗

Asymptomatic cerebrovascular lesions detected by magnetic resonance imaging in patients with systemic lupus erythematosus lacking a history of neuropsychiatric events.

OBJECTIVE: To clarify the extent of asymptomatic cerebrovascular involvement in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Cerebral magnetic resonance imaging (MRI) findings and ultrasonography findings of 100 patients with SLE lacking present or past clinical neurologic deficits were compared with 66 age-matched volunteers to determine the combined intima-media thickness (IMT) of the common carotid artery, and tests for anti-cardiolipin antibodies (aCL). RESULTS: Thirty-eight patients, but only 2 controls, showed imaging abnormalities. Among 23 SLE patients with cerebrovascular lesions by MRI who underwent single-photon emission computed tomography (SPECT), 14 showed hypoperfusion of the lesion. The IMT value and prevalence of aCL did not differ between the 55 SLE patients tested and controls. SLE disease activity index (SLEDAI) as assessed by a quantitative clinical index was significantly greater in patients with brain lesions than in those without. CONCLUSION: The prevalence of asymptomatic brain lesions in SLE patients is highs and shows a relationship to disease activity.

Adolescent↗

[Primary Sjögren's syndrome presenting as unconsciousness associated with IgA-lambda M-protein].

We describe the case of a 43-year-old woman who presented with primary Sjögren's syndrome (SS) which manifestated as unconsciousness due to M protein. A diagnosis of SS was made based on a ten-year history of dryness, a Shirmer test, and the histological findings of labial biopsy. A rouleaux formation was observed and serum protein electrophoresis revealed a monoclonal spike of 4.0 gm/dl in the gamma-region, which was characterized as IgA-lambda. Biopsy of the minor salivary glands showed marked polyclonal lymphoproliferation with lymphoid follicles, including both T cells and B cells as revealed by immunohistological staining. Therefore, the patient had a lymphoproliferative lesion of the minor salivary glands, which is also known as pseudolymphoma. We conclude that fainting associated with marked M protein may be manifestation of SS. Such cases should be followed carefully since the subsequent neoplastic transformation of pseudolymphomas have been previously reported.

Female↗

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

BACKGROUND: Lupus nephritis is a common manifestation of systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis has not been fully understood; however, immunological abnormalities have been considered in the development and activity of lupus nephritis. As angiotensin-converting enzyme (ACE) is implicated in various immunological phenomena, we investigated the correlation between insertion (I)/ deletion (D) polymorphism of the ACE gene and the activity of lupus nephritis. PATIENTS AND METHODS: Eighty-four patients with SLE and 100 healthy subjects were enrolled in this study. Following the extraction of genomic DNA from the peripheral blood, the ACE genotype was determined by the polymerase chain reaction. The patients were classified by the histological findings according to the WHO classification. In addition, the activity index and chronicity index were used to assess the severity of renal involvement. RESULTS: Individuals with II genotype showed a significantly increased activity of lupus nephritis. The allelic frequency was I/D = 0.84/0.16 in patients with WHO class IV renal lesions, and I/D = 0.36/0.64 in those with WHO class I lesions and 0.61/0.39 in patients with WHO class I or WHO class II. The difference in the allelic frequency between patients with WHO class IV and those with WHO class I or WHO class I + WHO class II was statistically significant (p = 0.00016 or p = 0.027, respectively). Moreover, lupus nephritis patients with II genotype showed significantly higher activity index than those with DD genotype (p = 0.0009). CONCLUSION: These results suggest that the insertion polymorphism of the ACE gene may correlate with the activity of lupus nephritis.

Adult↗

The first Japanese family with Sebastian platelet syndrome.

This report describes the first Japanese family diagnosed with Sebastian platelet syndrome. Within this family, a 6-year-old boy and 3 family members on his paternal side demonstrated thrombocytopenia with giant platelets and inclusion bodies in granulocytes, but the additional clinical features of Alport's syndrome occurring in the Fechtner syndrome were lacking. Light microscopy and ultrastructural findings of the leukocyte inclusion bodies distinguished these patients from the May-Hegglin anomaly. This family showed consistently higher levels of platelet-associated IgG (PAIgG), while surface expression of platelet membrane glycoproteins (GPIIb/IIIa and GPIb) and plasma glycocalicin levels were within the normal range. Careful observation of the giant platelet and leukocyte inclusion bodies in blood smears may help the diagnosis of this rare disease entity.

Adult↗

[Malignant tumors in childhood].

With the consistent use of effective multimodal treatment, including combination chemotherapy, surgery and radiotherapy, the prognosis for all types of childhood cancer has dramatically improved over the last 25 years and the current 5-year survival rate is about 60-98%. Concurrently, developments in the laboratory have improved our understanding of the biology of childhood malignancies. The availability of new imaging techniques, particularly advances in magnetic resonance imaging, have enabled more accurate assessments of tumor extent and staging. Such imaging techniques are now routinely used in radiotherapy planning to maximize treatment to tumor sites, while minimizing the exposure of normal tissues. Progress in surgery has allowed for better reconstructive techniques to repair defects created by tumor resections. The availability of blood component transfusions and hematopoietic cytokines, and advances in supportive care such as isolation techniques and preventive high-dose antibiotic therapy for infections, have allowed for the administration of increasingly intensive chemotherapies. Advances in our understanding of hematopoietic stem cells have enabled for significant extension of the techniques of bone marrow transplantation. Many of the advances in diagnosis, treatment, and our understanding of the biology of childhood cancers have emerged from studies conducted at centers with the required expertise, where multidisciplinary teams are available to coordinate the diagnosis, treatment, supportive care, and follow-up of children with cancer. The increasing population of children who survive into adulthood has renewed concern for the long-term consequences of therapy. Current studies focus on "risk-adapted" therapy, where the most intensive treatment is reserved for patients at highest risk of treatment failure, whereas treatment of children with a more favorable prognosis is designed to minimize the acute and late toxicities of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Combined multimodal therapy for osteosarcoma--neoadjuvant chemotherapy].

Until the 1970s, the survival rate of osteosarcoma patients was less than 20%. By the 1990s, this had improved to 60% to 70%, and limb-sparing procedures have replaced amputation in many patients thanks to effective combination therapy. Neoadjuvant chemotherapy has become an accepted practice in the majority of institutions using protocols which include MTX, ADR, BCD and CDDP as the most active agents against this disease. Newer agents, particularly IFM and ETP, are increasingly incorporated into complex regimens. While several studies have reported multivariate analyses to identify prognostic factors, the histologic response to preoperative chemotherapy remains the most important prognostic factor. Pulmonary metastases are the primary cause of death in patients with osteosarcoma. Although current treatment regimens allow effective salvage therapy for the patients with pulmonary metastases, the actuarial survival rate is 30%. A more effective systemic treatment for those patients is needed. The current management of osteosarcoma is critically reviewed and a treatment strategy is proposed for discussion.

Antineoplastic Combined Chemotherapy Protocols↗

[Elderly dyserythropoietic anemia first diagnosed after presentation of hemorrhagic gastric ulcer].

A 71-year-old man presented with epigastralgia and tarry stool. Laboratory examination showed anemia (Hb 7.1 g/dl) due to hemorrhagic gastric ulcer and positive Coombs' test without features of hemolysis. Initial bone marrow smears disclosed normal granulocytes and megakaryocytes, but only erythroid hyperplasia with multinuclearity and megaloblastosis was identified. Cytogenetic studies revealed normal karyotype. Congenital dyserythropoietic anemia (CDA) type II was initially suspected. Serologically, however, acid hemolysis and anti-I * i tests were negative as were the results of another Coombs' test. The second bone marrow aspiration disclosed a marked decrease in multinucleated erythroblasts together with an increase in those that had internuclear chromatin bridges. Electron microscopy of bone marrow specimens demonstrated morphological features of CDA types I and II, thus yielding a final diagnosis of elderly dyserythropoietic anemia, which is similar to both CDA types. It was suggested that the reactive secretion of erythropoietin due to bleeding played a role in these pathologic changes.

Aged↗

Phylogenic analysis of echovirus type 30 isolated from a large epidemic of aseptic meningitis in Japan during 1997-1998.

During 1997 to 1998, a nationwide epidemic of aseptic meningitis occurred in Japan. More than 4,500 isolates from patients with aseptic meningitis were identified as echovirus type 30. To investigate the character of these isolates, we examined the nucleotide sequences of thirty-seven geographical representatives and compared them with 50 strains isolated during the past 20 years. The phylogenic analysis used partial sequences from either the VP1 or VP4-VP2 region of the viral capsid. This analysis revealed that the isolates were divided into six genomic groups. All isolates identified during 1997-1998 belonged to only two genomic groups; these two groups are thought to be the causative viral agents involved in the recent epidemic.

Enterovirus B, Human↗

[A case of systemic lupus erythematosus discovered from left heart failure due to lupus induced mitral regurgitation].

A 50-year-old female was admitted to a local hospital because of dyspnea, and diagnosed as having left heart failure secondary to mitral regurgitation. After the improvement of congestive heart failure, polyarthralgia, fever, and positive anti-nuclear antibody were pointed out. She was referred to our hospital for the further evaluation. Serological test showed anti-double stranded DNA antibodies, anti-SS-A antibodies, anti-beta 2-GPI antibodies and biological false positive for syphilis. The diagnosis of SLE has been made from the clinical signs and the serology. Therefore mitral valvular lesion of this patient was considered to be one of the symptoms of SLE. We reported a rare case in which left heart failure was a initial clinical manifestation of SLE.

Female↗