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Biomedical subjects

T Fukushima

Publications and source records attributed to T Fukushima.

At least 91 records · Page 5Linked to original sources

Preparation of and tissue response to DNA-lipid films.

DNA-containing films have the potential to form complexes with antibiotics or cytokines by intercalation or groove-binding. This principle can be highly relevant for regenerative wound-healing around oral implants and in periodontology. In this study, we prepared DNA-lipid films and examined tissue responses to them as an indicator of their biological properties. The lipids were synthesized from the reaction of L-alanine, n-alkyl alcohol, and p-toluenesulfonic acid. We prepared the self-standing, water-insoluble DNA-lipid films by casting the DNA-lipid complex from chloroform/ethanol solution. The DNA-lipid complexes, which had 1:1 ratios of phosphate anions to cationic lipid, were found to have a double-helical B-form structure. The DNA-lipid films were almost dissolved 3 days after subcutaneous implantation in the backs of rats. There were no inflammatory reactions or inhibition of new tissue formation. We concluded that DNA-lipid films can be prepared by simple methods, and that they do not cause an unfavorable tissue response.

Absorbable Implants↗

Modified immunoregulation associated with interferon-gamma treatment of rat glioma.

Little is known about modulation by cytokines of major histocompatibility complex (MHC) antigen expression on intracranial tumors in vivo. The ability of cytokines to up-regulate MHC class-1 (MHC-1) antigen expression was investigated first in vitro using three rat glioma cell lines. Immunohistochemistry showed that incubation with recombinant rat interferon-gamma (rrIFN-gamma) increased MHC-1 antigen expression in RG2, C6, and 9L cell lines. Flow cytometric analysis revealed different baseline levels of MHC-1 antigen expression in each line (RG2 lowest, C6 highest), and that these levels increased in all lines after stimulation with 100 U ml(-1) or more of rrIFN-gamma. The antitumor effect of rrIFN-gamma in vivo was evaluated by assessing survival of rats with implanted intracerebral RG2 gliomas after intracarotid infusion of rrIFN-gamma. A high dose of rrIFN-gamma (2.4 x 10(5) U kg(-1)) significantly increased the survival, compared to control (p < 0.02). Intracarotid pre-treatment with the bradykinin analogue RMP-7 did not further increase survival. Immunohistochemical staining of tumor sections after in vivo rrIFN-gamma, infusion showed no clear increase in MHC-1 antigen expression on tumor cells but increased staining for ED2 antigen within tumor tissue, presumably from perivascular cells with MHC class-2 antigen.

Animals↗

Participatory assessment of the environment from children's viewpoints: development of a method and its trial.

To understand the actual viewpoints of children about daily life and the environment, the authors, adopting a participatory strategy, visited 21 classes of Japanese school children, improved in a stepwise process their ways of question-asking, and developed "WIFY"(what is important for you); a set of interactive questions composed of a basic question and three accompanying instructions. In applying WIFY, 59 fourth graders, 22 in Nagasaki, Japan and 37 in Beijing, China, reported their viewpoints in each of classroom settings. In both settings, when children were allowed to communicate with each other by the use of WIFY answering sheet, spontaneous exchanges arose and continued. WIFY itself is supposed to bring out and enhance mutual collaboration and spontaneous networking. In this instance, WIFY functioned as a communication tool. When answering sheets were collected and obtained responses were analyzed as cases, a rather materialistic view was suggested among Japanese children and a more disciplined view, which put much value on school and home, was suggested among Chinese children. Further studies are needed to confirm the changing environmental views of children from the collaborative research framework.

Attitude↗

Expression of nuclear factor-kappa B, tumor necrosis factor receptor type 1, and c-Myc in human astrocytomas.

Tumor necrosis factor receptor type 1 (TNFR1) and c-Myc are important in signal transduction in tumor necrosis factor-alpha (TNF-alpha)-induced cytotoxicity, whereas activation of nuclear factor-kappa B (NF-kappa B) protects against TNF-alpha-induced apoptosis. This study investigated the expression of NF-kappa B, TNFR1, and c-Myc in human astrocytoma tissues by reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemical analysis. TNFR1 messenger ribonucleic acid (mRNA) and c-Myc mRNA were frequently expressed in malignant astrocytomas, especially in glioblastomas, compared with low-grade astrocytomas by PCR analysis. TNFR1 and c-Myc mRNAs were barely detectable in normal brain tissues. NF-kappa B p50 and p65 subunit mRNAs were detected in various grades of astrocytomas, with frequent expression in malignant astrocytomas. The presence of activated NF-kappa B was confirmed by nuclear localization in neoplastic astrocytes as determined by immunohistochemistry. Both p50 and p65 subunits were inhomogeneously expressed in neoplastic astrocytes of glioblastoma, but only in a few scattered tumor cells in low-grade astrocytoma, and almost undetectable in normal brain tissues. These results indicate that TNFR1 and c-Myc are overexpressed in malignant astrocytomas, and this may increase the cellular sensitivity to the cytotoxic action of TNF-alpha. NF-kappa B p50 and p65 were simultaneously induced and activated in malignant astrocytomas. Our results suggest that the constitutive activation of NF-kappa B subunits in malignant astrocytoma, especially in glioblastoma, could be associated with the resistance to TNF-alpha immunotherapy, and indicates new therapeutic strategies for malignant astrocytomas.

Antigens, CD↗

Squamous cell carcinoma arising in an intracranial dermoid cyst--case report.

A 47-year-old male presented with headache. Magnetic resonance imaging revealed an enhanced mass lesion in the cerebellar vermis and left cerebellar hemisphere and in the cisterna magna. Gross total removal of the tumor was performed. Histological examination demonstrated squamous cell carcinoma in the dermoid cyst. The patient subsequently received localized radiation therapy of total 55 Gy. He has been without tumor recurrence for 6 years since the surgery. We recommend local radiation therapy over 50 Gy following surgery.

Carcinoma, Squamous Cell↗

Large cholesterol granuloma arising from the frontal sinus--case report.

A 59-year-old male presented with a large cholesterol granuloma arising from the frontal sinus manifesting as a large, fluctuated, soft mass in his brow, compressing left eye. Skull radiography showed dilation of the frontal sinus. Computed tomography and magnetic resonance imaging revealed a cystic mass extending into the left orbit and anterior cranial fossa. Gross inspection at the frontal craniotomy showed mucinous, dark green fluid intermingled with shining material. The histological diagnosis was cholesterol granuloma with epithelial lining. Large cholesterol granuloma with facial deformity is always associated with bone and cosmetic problems. Wide opening of the frontal sinus followed by cyst wall removal and plastic repair of the skull is necessary.

Cholesterol↗

Colorectal carcinogenesis.

Colorectal carcinogenesis is a multi-step process during which genetic and epigenetic events determine the transition from a normal cell to a malignant cell. In the past decade, intensive research led to the identification of two types of colorectal cancers that are distinct by their carcinogenesis process. The first group, named LOH (Loss of Heterozygosity) type, is characterized by allelic losses of tumor suppressor genes. The second group, called MSI (Microsatellite Instability) type, is characterized by genetic instability at microsatellite loci. In addition, recent studies suggest the four different signaling pathways, Wnt/Wingless pathway, K-ras pathway, TGF-beta pathway and p53 pathway, could be implicated in tumor progression. In this review we discuss the development of colorectal cancer on the basis of molecular biology and recent advances in research of the colorectal cancer.

Colorectal Neoplasms↗

[Complex translocation (8;15;21) (q22;p12;q22) in a child with AML-M2 showing de novo appearance of the short form of AML1-MTG8 chimeric mRNA during the course].

A 4-year-old boy admitted with exophthalmos was diagnosed as having acute myeloblastic leukemia with maturation (AML-M2). Chromosomal analysis (G-banding) showed t(8;15;21). Fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), spectral karyotyping (SKY), and nucleolar organizer region (NOR) staining suggested that this complex translocation might have resulted from stepwise translocation, namely an initial translocation between chromosomes 8 and 21, followed by a second translocation between der(21) and chromosome 15, rather than the other possibility of clockwise translocation. During chemotherapy, RT-PCR demonstrated the short form of AML1-MTG8 mRNA, in addition to chimeric mRNA of the usual length. Sequence analysis revealed that this shorter chimeric mRNA had resulted from deletion of a 250-bp sequence at the 5' end of MTG8. A literature search failed to reveal any similar cases of t(8;21) AML-M2 associated with this deletion of chimeric mRNA.

Base Sequence↗

Improved interactive medical and public health education in Japan and Korea.

We have carried out case based comparative studies in Japan, US and Korea with special reference to the medical education programme using standardized patients (SPs). The schools in US we have visited are still in the process further reforming interactive medical education. In Daegu, Korea, five medical schools have jointly started a working group for the betterment of medical education on a regular basis from the year 1999. The emphasis is on cooperative research on standardized patient training and its application. In Japan, the substantial activities for training and implementing SPs were later followed by several citizens who are active in training and providing SPs to medical schools and hospitals in need. In comparison to the established research oriented framework and flexible application of SPs in US and new & dynamic developmental discussions of SPs in Korea, the Japanese reality is a bit behind with less opportunity for research oriented trials.

Competency-Based Education↗

Occurrence and determination of a natriuretic hormone, 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxy chroman, in rat plasma, urine, and bile.

The occurrence of a new natriuretic hormone, 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxy chroman (LLU-alpha, gamma-CEHC) in rat plasma was demonstrated and its concentration was determined using a coupled-column HPLC with a fluorometric derivatization with 4-N,N-dimethylaminosulfonyl-7-piperazino-2,1,3-benzoxadiazol e (DBD-PZ) followed by O-acetylation. The concentration of LLU-alpha was 328 +/- 113 nM in rat plasma (N = 5). LLU-alpha was found in not only urine, but also bile, suggesting an enterohepatic circulation in body. We also assigned the configuration at C-2 of LLU-alpha in these biological fluids as (S)-form by an HPLC with a chiral column. The LLU-alpha concentration decreased significantly by fasting for 3 days (P < 0.01). These results support the possibility that LLU-alpha is produced from gamma-tocopherol in diet via oxidative metabolism without racemization.

Animals↗

A post-traumatic ligamentum flavum progressive hematoma: a case report.

STUDY DESIGN: A case report. OBJECTIVES: To understand a rare case of ligamentum flavum progressive hematoma. SUMMARY OF BACKGROUND DATA: Previously there were only two reports about ligamentum flavum hematoma. METHODS: A patient was surgically treated for ligamentum flavum hematoma causing progressive L5 radiculopathy. Clinical and neuroradiologic features were reported, and the literature was reviewed. RESULTS: The etiology of this case could not be defined except by minor back injury. In spite of conservative therapy, the symptoms were progressive for 7 months. Magnetic resonance imaging demonstrated the epidural mass lesion at L4-L5 that was continuous with the ligamentum flavum. The mass was hypointense in T1-weighted images and central hyperintense and marginal hypointense in T2-weighted images. The margin was well enhanced by Gd-DTPA administration. After removal of the mass lesion, the patient's symptoms completely resolved. Before surgery, accurate diagnosis was difficult even based on magnetic resonance imaging and was achieved after histologic examinations. CONCLUSIONS: Surgery could be a choice of the treatment modality to resolve symptoms in ligamentum flavum hematoma.

Hematoma↗

Dynamic mediolateral activation of the pyramidal cell population in human somatosensory 3b area can be visualized by magnetic recordings.

Dynamic mediolateral activation in the pyramidal cell population of the human somatosensory 3b area was studied non-invasively. Somatosensory evoked fields (SEFs) were recorded over the hand area contralateral to the right median nerve stimulation at the wrist. Localization of an equivalent current dipole (ECD) for N20m primary cortical response was successively calculated for periods of 2.4 ms around N20m peak where the signal-to-noise ratio exceeded 100 and the spatial resolution was approximately 0.3 mm. The ECD moved toward the anterior, lateral and inferior direction for a distance of 8.7 mm at a propagation velocity of 3.6 m/s. This direction was orthogonal to the orientation of apical dendrites of the pyramidal neurons in area 3b and parallel to the surface of the posterior bank of the central sulcus. These findings suggest that the sequential mediolateral activation of the pyramidal cells in the somatosensory cortex is mediated by horizontal connections running parallel to the cortical surface.

Adult↗

Identification of a melanoma antigen, PRAME, as a BCR/ABL-inducible gene.

In order to elucidate molecular events in BCR/ABL-induced transformation, we adopted a polymerase chain reaction (PCR)-based technique of differential display and compared mRNA expression in human factor-dependent cells, TF-1, with that in factor-independent cells, ID-1, which were established from TF-1 cells by transfection of BCR/ABL. Cloning and sequencing of a gene which was upregulated in ID-1 cells revealed that the gene was identical to a melanoma antigen, PRAME. Our present study demonstrated that PRAME was markedly expressed in primary leukemic cells with chronic myeloid leukemia (CML) in blastic crisis and Philadelphia (Ph)+-acute lymphoblastic leukemia (ALL), in which BCR/ABL played an important role as a pathogenic gene. Moreover, comparison of PRAME expression among CD34+ cells with CML in blastic, accelerated, and chronic phases revealed a higher expression in CML in advanced phases. Thus PRAME was considered to be a good candidate for a marker of Ph+-leukemic blast cells as well as a new target antigen of leukemic blast cells that cytotoxic T cells can recognize.

Antigens, Neoplasm↗

Sensitive determination of anandamide in rat brain utilizing a coupled-column HPLC with fluorimetric detection.

A fluorimetric determination method for N-arachidonoylethanolamine (anandamide) was developed using a precolumn fluorescence derivatization followed by coupled-column high-performance liquid chromatography (HPLC). Anandamide extracted from the rat brain tissue was derivatized with 4-N-chloroformylmethyl-N-methylamino-7-N, N-dimethylaminosulfonyl-2,1,3-benzoxadiazole (DBD-COCl), purified by a solid-phase extraction (Emporetrade mark), and assayed by the coupled-column HPLC. The HPLC consisted of phenyl (100 x 4.6 mm i.d. ) and octadecylsilica columns (250 x 4.6 mm i.d.), both connected by a six-port valve. The concentration of anandamide in rat brain was 3. 37 +/- 0.73 pmol/g with 6.47 and 3.57% of intra- and inter-day precisions, respectively. Using this method, we investigated the alteration of anandamide concentration in rat brain 30 min after administration of anandamide (2 mg/kg, i.p.) to rats pretreated with or without phenylmethylsulfonyl fluoride (PMSF; 30 mg/kg, i.p.), an inhibitor of amidohydrolase. In rats pretreated with PMSF, the brain concentration of anandamide was approx. 16-fold higher than that of rats without PMSF (p < 0.01).

Animals↗

Feasibility of a novel weekday-on/weekend-off oral UFT schedule as postoperative adjuvant chemotherapy for colorectal cancer. UFT Compliance Study Group, Kanagawa, Japan.

PURPOSE: When oral anticancer agents are used for adjuvant chemotherapy of colorectal cancer, compliance and feasibility become issues because of the long treatment time. Appropriate studies of these issues are lacking. We investigated compliance and feasibility during a weekday-on/weekend-off schedule of oral UFT (uracil-tegafur) over a period of 1 year administered as adjuvant chemotherapy to patients with colorectal cancer. PATIENTS AND METHODS: A UFT dose of 600 mg/day was prescribed according to a weekday-on/weekend-off schedule to 87 patients after potentially curative resection. Compliance was investigated in three ways: physician interview, patient self-report, and chemical analysis of urine. The results were compared with the dose prescribed. Feasibility was evaluated on the basis of two indices: relative performance (RP), which was the ratio of the actual total dose taken to the total dose planned, and individual dose intensity (IDI), which was the ratio of the actual dose taken to the dose planned during a given period. RESULTS: The compliance assessed by physician interview and by patient self-report conformed well with the prescribed dose, the rate of agreement among the three compliance measures being more than 94%. Chemical analysis of urine in 38 of the patients revealed that they were actually taking the drug. The RP was 0.72, and the IDI was 0.8. CONCLUSION: From these results, the feasibility of the weekday-on/weekend-off schedule was judged to be good. It is suggested that the feasibility would be even better if the dose of UFT was set according to body surface area.

Administration, Oral↗

Juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease) with diffuse neurofibrillary and lewy body pathology.

We describe an unusual case of Hallervorden-Spatz disease (HSD). After presenting with limb rigidospasticity at the age of 9 years, our patient developed progressive dementia, spastic tetraparesis and myoclonic movements, leading to akinetic mutism. He died of pneumonia at the age of 39 years. Autopsy revealed a severely atrophic brain, weighing 510 g. Histologically, there were iron deposits in the globus pallidus and substantia nigra pars reticulata, and numerous axonal spheroids throughout the brain and spinal cord. Neurofibrillary tangles were abundant in the hippocampus, cerebral neocortex, basal ganglia and brain stem. Neuritic plaques and amyloid deposits were absent. Lewy bodies and Lewy neurites, which were immunolabeled by anti-alpha-synuclein, were found in the brain stem, cerebral cortex and spinal gray matter. Sarkosyl-insoluble tau extracted from the temporal cortex resolved on immunoblots into three major bands of 60, 64 and 68 kDa and a minor band of 72 kDa, as reported for Alzheimer's disease. The present case, together with a few similar cases reported previously, may represent a particular subset of neuroaxonal dystrophy, i.e., HSD associated with extensive accumulation of both tau and alpha-synuclein.

Adolescent↗

The incidence and outcome of pelvic sepsis following handsewn and stapled ileal pouch anal anastomoses.

The incidence and outcome of pelvic sepsis was analyzed in 210 patients who underwent restorative proctocolectomy for ulcerative colitis (UC) in 197 patients, and for familial adenomatous polyposis (FAP) in 13 patients. Pelvic sepsis developed in 18 patients (8.6%) and a significantly higher incidence was seen in men than in women, at 13.6% vs 3.7%, respectively (P < 0.05). The incidence of pelvic sepsis in patients with UC complicated by toxic megacolon and/or fulminant colitis was significantly higher that in those without any preoperative complications, at 36.4% vs 7.4% (P < 0.05). The incidence of pelvic sepsis following handsewn anastomosis was significantly higher than that following stapled anastomosis, at 15.6% vs 5.5% (P < 0.05). The outcome of pelvic sepsis in patients with a stapled anastomosis was better than that in those with a handsewn anastomosis. The prognosis of women who developed pelvic sepsis was better than that of men who developed pelvic sepsis. The risk factors predisposing to pelvic sepsis were UC, especially when complicated by toxic megacolon and/or fulminant colitis, and male sex, while a handsewn anastomosis was more vulnerable than a stapled anastomosis.

Adenomatous Polyposis Coli↗