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Biomedical subjects

E Kobayashi

Publications and source records attributed to E Kobayashi.

At least 235 records · Page 13Linked to original sources
PubMed1996

Synthesis and antitumor activity of duocarmycin derivatives: modification of segment A of duocarmycin B2.

Several A-ring pyrrole derivatives of duocarmycin B2 were synthesized effectively from the 3-hydroxy compounds by utilizing an interesting acid-catalyzed rearrangement, their anticellular activity was preliminarily evaluated by assays of growth inhibition of HeLa S3 cells (in vitro) and antitumor activity against murine sarcoma 180 (in vivo). The 8-O-N,N-dialkylcarbamoyl derivatives of the A-ring pyrrole compound showed remarkably potent in vivo antitumor activity, superior to that of duocarmycin B2. these derivatives were subjected to further biological evaluation. They exhibited potent antitumor activity toward murine solid tumors including M5076 sarcoma, B-16 melanoma and Colon 26 adenocarcinoma. Their most noteworthy feature was their efficacy against various human xenografts including LC-6 (lung), St-4 (stomach), and Co-3 (colon).

Animals↗
PubMed1996

Conversion of a cyanhydrin compound into S-(-)-3-phenyllactic acid by enantioselective hydrolytic activity of Pseudomonas sp. BC-18.

A Pseudomonas strain, named BC-18, which can convert racemic phenylacetaldehyde-cyanhydrin (3-phenyllactonitrile) enantioselectively to S-(-)-3-phenyllactic acid (S-PLA), was isolated from soil. Although PLA produced with intact cells contained the S enantiomers of approximately 75% enantiomeric excess (% e.e.), repeated crystallization gave a higher purity (99.8% e.e.) of the S configuration product. Production of S-PLA was significantly increased when 2.0% (w/v) of calcium chloride were added to the reaction mixture for precipitation of S-PLA. Chemical mutagenesis yielded a mutant strain, named BC348-9, with 16 times higher activity (40 mU/OD630), compared with that of the parent strain (2.5 mU/OD630). When the mutant strain BC348-9 was used, approximately 18 g/OD630 was produced, which is 12 times higher than that of the parent strain. The final accumulation of PLA exceeded 6.0%, 1.2 times higher than that of the parent strain.

Calcium Chloride↗
PubMed1996

Posterior fusion for odontoid fracture in an infant--case report.

A 2-year-3-month-old girl presented with a rare displaced odontoid fracture. She was managed nonoperatively by manipulation followed by 3-month extracorporeal fixation with a halo brace. However, lateral radiography revealed recurrent dislocation at the base of the odontoid process. Magnetic resonance imaging demonstrated a "synchondrotic slip." She therefore underwent posterior wiring with iliac bone grafting to prevent pseudoarthrosis. The odontoid process had fused to the axis at 4 months postoperatively. Surgical management should be considered as a treatment method for pediatric odontoid fracture because of the difficulties in maintaining long-term immobilization and confirming the union.

Child, Preschool↗
PubMed1996

Dural cavernous angioma causing acute subdural hemorrhage--case report.

A 78-year-old female presented with a nontraumatic acute subdural hematoma (ASDH) caused by hemorrhage from a cavernous angioma located on the convexity dura mater. The hematoma and angioma were removed successfully. Neuroimaging performed 2 years previously had not revealed cavernous angioma. The angioma most likely grew rapidly over the 2 year period, during which she had received oral antiplatelet medication. Nontraumatic ASDH may originate from a cavernous angioma which grows rapidly.

Aged↗
PubMed1996

[A case of spontaneous rhinorrhea detected by SPAMM-tagging method].

This is the first report of rhinorrhea detected by special modulation of the magnetization (SPAMM)-tagging method. A 54-year-old male was admitted to our hospital for treatment of right rhinorrhea which had continued for 2 months and a half. The CSF leakage was induced by specific head position and the volume was more than 50 ml a day. Metrizamide CT cisternography revealed the contrast medium in the lateral extension of the right sphenoid sinus. MRI demonstrated liquorrhea with abnormal intensity of the sinus. 3D-CT revealed bony defects at the temporal base. Operation revealed herniated brain through the same bony defect of the temporal base into the extended sphenoid sinus. Post-operative diagnosis was Morley's rhinorrhea. The leakage point was closed and patched with the femoral fascia. Preoperative SPAMM-tagging image with cine MRI was useful to identify the responsible leakage point as a disorder of lattice tags. This method is a kind of flowmetry with MRI and is very effective because it can detect non-invasively slight CSF motion into the sinuses. It can also detect the direction and rough flow volume of rhinorrhea, so may also predict the risk of meningitis. The disadvantages were also discussed.

Cerebrospinal Fluid Rhinorrhea↗
PubMed1996

Antitumor activities of combined treatment with a novel immunomodulator, (2S,3S,4R)-1-O-(alpha-D-Galactopyranosyl)-2-(N-Hexacosanoylamino)-1,3,4 - octadecanetriol (KRN7000), and radiotherapy in tumor-bearing mice.

The novel immunomodulator (2S,3S,4R)-I-O-(alpha-D-galactopyranosyl)-2- (N-hexacosanoylamino)-1,3,4-octadecanetriol (KRN7000) in combination with high-dose (20 and 30 Gy) local x-ray irradiation or low-dose (3 Gy) fractionated whole-body irradiation showed significantly stronger antitumor activities against Meth A-and Colon26-bearing mice than treatments by radiation or KRN7000 alone, and 60% of mice in combination treatment groups were cured. Furthermore, the results of tests rechallenging the cured mice with Meth A and Colon26 cells strongly suggested that tumor-specific immunity was induced by the combination treatment. The suggestion was supported by the result that the systemic administration of KRN7000 could produce large amounts of interleukin-2 and interferon-gamma, which contribute to induction of tumor-specific cytotoxic lymphocytes not only in normal mice but also in whole-body irradiated mice. Furthermore, it was also suggested that KRN7000 contributes to protecting antitumor effector cells, such as natural killer cells, from impairments caused by radiation. Taking together the results and the knowledge that tumor-specific cytotoxic lymphocytes play a critical role in prevention of tumor recurrence and distant metastasis, it is strongly suggested that combined therapy with KRN7000 and radiation could be quite useful for cancer treatment.

Adjuvants, Immunologic↗
PubMed1996

Enhancing effects of (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-2-(N-hexacosanoylamino) -1,3,4-octadecanetriol (KRN7000) on antigen-presenting function of antigen-presenting cells and antimetastatic activity of KRN7000-pretreated antigen-presenting cells.

(2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-2-(N-hexacosanoylamino)- 1,3, 4-octadecanetriol (KRN7000), with an alpha-galactosylceramide structure, is an immunomodulator showing potent antimetastatic activities. In an in vitro study, KRN7000 potently stimulated proliferation and enhanced natural killer activity in spleen cells from BALB/c euthymic mice, but not BALB/c athymic (nu/nu) mice, suggesting that T cells play an important role in these activities. To study the detailed immunostimulatory mechanisms of KRN7000, syngeneic mixed leukocyte reactions were then performed using dendritic cell-enriched fractions (DCEFs) from spleens of BALB/c euthymic and athymic mice. In these studies, KRN7000 enhanced the antigen-presenting cell activities of the DCEFs. In addition, marked production of interleukin-2 and interferon-gamma in BALB/c euthymic mice was observed following treatment with KRN7000 in vitro and in vivo. Because of these strong immunostimulating effects of KRN7000, its antimetastatic effects were also evaluated. Adoptively transferred KRN7000-treated DCEF markedly prolonged the survival time of mice bearing B16 pulmonary metastases. These results demonstrate that KRN7000 may be useful for cancer therapy not only as an antitumor agent but also as an activator of antigen-presenting cells such as dendritic cells, which can be used for adoptive cellular therapy.

Adjuvants, Immunologic↗
PubMed1995

Improved genomic/nuclear DNA extraction for 8-hydroxydeoxyguanosine analysis of small amounts of rat liver tissue.

Using two different commercially available extraction kits, genomic/nuclear DNA could be recovered from rat liver samples as small as 10 mg. Background 8-hydroxydeoxyguanosine levels in such DNA were low and stable at 0.26-0.30 +/- 0.01-0.03/10(5) guanine residues. The minimum tissue wet weight required for the accurate 8-hydroxydeoxyguanosine analysis was 25 mg. The present results indicate that routine and reliable assessment of the involvement of oxidative DNA damage in the development of various diseases, including cancer, is feasible using a variety of tissue sources.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

cDNA structure, alternative splicing and exon-intron organization of the predisposing tuberous sclerosis (Tsc2) gene of the Eker rat model.

The Eker rat hereditary renal carcinoma (RC) is an excellent example of a Mendelian dominant predisposition to a specific cancer in an experimental animal. We recently reported that a germline insertion in the rat homologue of the human tuberous sclerosis gene (TSC2) gives rise to the dominantly inherited cancer in the Eker rat model. We now describe the entire cDNA (5375 bp without exons 25 and 31) and genomic structure of the rat Tsc2 gene. The deduced amino acid sequence (1743 amino acids) shows 92% identity to the human counterpart. Surprisingly, there are a great many (> or = 41) coding exons with small sized introns spanning only approximately 35 kb of genomic DNA. Two alternative splicing events [involving exons 25 (129 bp) and 31 (69 bp)] make for a complex diversity of the Tsc2 product. The present determination of the Tsc2 gene and establishment of strong conservation between the rat and man provide clues for assessing unknown gene functions apart from that already predicted from the GTPase activating proteins (GAP3) homologous domain and for future analysis of intragenic mutations in tumors using methods such as PCR-SSCP and for insights into diverse phenotypes between species.

Alternative Splicing↗
PubMed1995

Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice.

Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2- [N-((R)-2- hydroxytetracosanoyl)-amino]- 1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application.

Animals↗
PubMed1995

Development of an MRI-compatible needle insertion manipulator for stereotactic neurosurgery.

A variety of medical robots for stereotactic neurosurgery has been developed in recent years. Almost of all these robots use computed tomography (CT) to scan the brain of the patient before and during surgery. Currently, we are developing a needle insertion manipulator for magnetic resonance imaging (MRI)-guided neurosurgery. MRI techniques, including MRI angiography and functional MRI, are attractive for the development of interventional MRI therapies and operations. If a robot were available, these therapies would be minimally invasive, with more accurate guidance than is possible with current CT-guided systems. Actuation of a robot in an MRI environment is difficult because of the presence of strong magnetic fields. Therefore, the robot must be constructed of nonmagnetic materials. The system frame was manufactured using polyethylene terephthalate (PET) and was actuated using ultrasonic motors. Accuracy-evaluation procedures and phantom tests have been performed. The total accuracy of the system was approximately 3.0 mm. No artifacts caused by the manipulator were observed in the images.

Brain↗