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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 379 records · Page 21Linked to original sources
PubMed1998

Fractionated stereotactic radiotherapy of small intracranial malignancies.

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) in patients with small intracranial malignancies. METHODS AND MATERIALS: From July 1991 to March 1997, 80 patients with a total of 121 brain or skull-base tumors were treated with FSRT alone, and were followed for periods ranging from 3 to 62 months (median 9.8). The majority of patients received 42 Gy in 7 fractions over 2.3 weeks, but in July 1993, protocols using smaller fraction doses were introduced for patients whose radiation-field diameters were larger than 3 cm or whose tumors were close to critical normal tissues. RESULTS: For 64 patients with metastatic brain tumors the overall median survival was 8.3 months and 1-year actuarial survival rate was 33%. Significant prognostic factors were: the presence of extracranial tumors, pre-treatment performance status, and the lung as a primary site. Patients without extracranial tumors prior to FSRT had a median survival of 21.2 months. For seven patients with high-grade glioma, 1-year actuarial local control rate was 75%, with a median survival of 10.3 months. For patients with skull-base tumors the local control was achieved in 6 of 6 patients (100%), with a median survival of 30.7 months. No one suffered from acute complications, but three patients, two of whom had undergone FSRT as the third course of radiotherapy, developed late radiation injuries. CONCLUSION: Overall high local control and low morbidity rates suggest that FSRT is an effective and safe modality, even for those with a history of prior irradiation. However, patients with risk factors should be treated with smaller fraction doses.

Analysis of Variance↗
PubMed1998

Optical responses evoked by single-pulse stimulation to the dorsal root in the rat spinal dorsal horn in slice.

Neuronal excitation evoked after dorsal-root (DR) stimulation in the spinal dorsal horn (DH) of rats was visualized with a high-resolution optical-imaging method, and the propagation mechanism was studied. Transverse slices of the spinal cord were obtained from 2-4 week-old rats and stained with the voltage-sensitive dye RH-482. Single-pulse stimulation to the primary-afferent A fibers in the DR attached to the slice evoked a weak, brief (<10 ms) excitatory optical response in the laminae I and III-V. When the stimulus intensity and duration were increased to activate both A and C fibers, an additional, much greater, and longer-lasting (>100 ms) excitatory response was generated in the laminae I-III, most intensely in the lamina II. A treatment with excitatory amino acid (EAA) antagonists, dl-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2, 3-dione, significantly reduced the amplitude and duration of the response in the lamina II. The optical response in the antagonists-containing solution was quite similar to that recorded in a Ca2+-free solution that blocked afferent synaptic transmission. The late component (>10 ms) was, however, slightly greater than that in the Ca2+-free solution. Treatment with the ATP-receptor antagonist, suramin, had a minimal effect on the response in the presence of EAA antagonists. These results suggested that the propagation of the DR-stimulus-elicited excitation was contributed largely by EAA receptors, but also by other receptors to a much lesser extent.

Animals↗
PubMed1998

Slow intrinsic optical signals in the rat spinal dorsal horn in slice.

Tetanic stimulation of high-threshold primary afferent fibers in the dorsal root was found to elicit intrinsic optical signals (IOSs) in transverse slices of 11- to 20-day-old rat spinal cords. The IOS, lasting for 30 s or longer, was most prominent in the lamina II of the dorsal horn. Treatment with a Na+-K+-2Cl- co-transport blocker, furosemide, abolished the IOS, suggesting that the origin of the IOS is the cellular swelling due to an activity-dependent rise in extracellular K+. Substance P antagonist spantide, glutamate antagonists 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, and the mu-opioid agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin suppressed IOSs. Thus, IOSs represent at least in part the slow excitatory response that is known to be generated in dorsal horn neurons after tetanic activation of unmyelinated afferent fibers.

2-Amino-5-phosphonovalerate↗
PubMed1998

Activated rat stellate cells express c-met and respond to hepatocyte growth factor to enhance transforming growth factor beta1 expression and DNA synthesis.

Hepatocyte growth factor (HGF) decreases transforming growth factor beta1 (TGFbeta1) levels in the liver and attenuates hepatic fibrosis caused by dimethylnitrosamine in rats. In the liver, HGF is presumed to act predominantly on parenchymal cells, and TGFbeta1 is produced mainly by mesenchymal cells. In hepatic fibrosis, stellate cells play a central role with undergoing activation, which also occurs when the cells are cultured on plastic. Thus, we wondered if HGF could act directly on stellate cells. c-Met was detected in rat stellate cells activated by culture for 10 days, but not in the cells cultured for 3 days. Specific binding of HGF to the activated cells was determined, and Scatchard analysis indicated an apparent Kd of 1.5 nM. c-Met mRNA was detected in freshly isolated stellate cells from rats treated with carbon tetrachloride for 8 weeks, but not in those cells from normal rats. These results indicate that stellate cells express c-met when activated in vitro and in vivo. HGF enhanced TGFbeta1 production and DNA synthesis in the activated cells.

Animals↗
PubMed1998

Predictors of sudden cardiac death in hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HC) die suddenly. Proposed risk factors for sudden cardiac death (SCD) in HC are youth, a family history of SCD, syncope, and ventricular tachycardia. Hemodynamic variables have not convincingly proved to be risk factors for SCD. Therefore, this study was designed to examine predictors of SCD in a large number of patients with HC during long-term follow-up periods. The relation of studied variables (clinical, electrocardiographic, echocardiographic, hemodynamic, and exercise test findings) to SCD in 309 patients with HC who were initially diagnosed during 1971 through 1994 (mean follow-up 9.4 years) was examined by multivariate analysis. SCD occurred in 28 patients. Independent predictors of SCD were a smaller difference between peak and rest systolic blood pressure during exercise testing (p=0.006), and higher left ventricular outflow tract pressure gradient at rest (p=0.003). Exercise-related SCD occurred in 8 patients and exercise-unrelated SCD in 20 patients (mean age 28 vs 47 years, p <0.05). Thus, patients of exercise-related SCD were younger and had smaller increases in systolic blood pressure during exercise testing, whereas patients with exercise-unrelated SCD were older and had higher left ventricular outflow tract pressure gradient.

Adolescent↗
PubMed1998

Cloning and characterization of human Sep1 (hSEP1) gene and cytoplasmic localization of its product.

We isolated and sequenced a human cDNA (designated as hSEP1) encoding both a homologue of mouse Dhm2 and budding yeast SEP1. The gene was shown to be located on the long arm of chromosome 3 (3q25-26.1). The putative hSEP1 product (hSEP1p) consisted of 1694 amino acid residues with a molecular mass of about 190 kDa. Northern blot analysis showed a major 10-kb mRNA expressed ubiquitously in various organs as well as a minor 5.5-kb mRNA expressed relatively highly in the testis and placenta. hSEP1p is localized in the cytoplasm as examined by cytochemical and Western blot analyses of fractionated cellular extracts. The biological function of hSEP1p was discussed in correlation with its cytoplasmic localization.

Amino Acid Sequence↗
PubMed1998

A novel hydrophobized polysaccharide/oncoprotein complex vaccine induces in vitro and in vivo cellular and humoral immune responses against HER2-expressing murine sarcomas.

To elicit specific cellular immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the MHC class I pathway constitutes a central issue. We report here a novel formula of hydrophobized polysaccharide nanoparticles, which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway. A protein consisting of the 147 amino-terminal amino acids of oncogene erbB-2/neu/HER2 (HER2) was complexed with two kinds of hydrophobized polysaccharides, cholesteryl group-bearing mannan (CHM) and cholesteryl group-bearing pullulan (CHP), to form nanoparticles (CHM-HER2 and CHP-HER2). CHM-HER2 and CHP-HER2 were able to induce CD3+/CD8+ CTLs against HER2-transfected syngeneic fibrosarcoma cell lines. In contrast, the oncoprotein alone failed to do so. These CTLs were Kd-restricted and specifically recognized a peptide (position 63-71) that was a part of a truncated HER2 protein used as an immunogen. In addition, vaccination by CHM-HER2 complexes led to a strongly enhanced production of IgG antibodies against HER2, whereas vaccination with HER2 proteins alone resulted in a production of antibodies at a marginal level. Mice immunized with CHM-HER2 or CHP-HER2 before tumor challenge successfully rejected HER2-transfected tumors. The complete rejection of tumors also occurred when CHM-HER2 was applied not later than 3 days after tumor implantation. In the effector phase of in vivo tumor rejection, CD8+ T cells played a major role. The results suggest that a sort of hydrophobized polysaccharide may help soluble proteins to induce cellular immunity as well enhance humoral immunity; hence, such a novel vaccine may be of potential benefit to cancer prevention and cancer therapy.

Animals↗
PubMed1998

Bloom's and Werner's syndrome genes suppress hyperrecombination in yeast sgs1 mutant: implication for genomic instability in human diseases.

Bloom's syndrome (BS) and Werner's syndrome (WS) are genetic disorders in which an increased rate of chromosomal aberration is detected. The genes responsible for these diseases, BLM and WRN, have been found to be homologs of Escherichia coli recQ and Saccharomyces cerevisiae SGS1 genes. Here we show that yeast Sgs1 helicase acts as a suppressor of illegitimate recombination through homologous recombination and that human BLM and WRN helicases can suppress the increased homologous and illegitimate recombinations in the S. cerevisiae sgs1 mutant. The results imply a role of BLM and WRN helicases to control genomic stability in human cells. Similar to Sgs1 helicase, BLM helicase suppressed the cell growth in the top3 sgs1 mutation background and restored the increased sensitivity of the sgs1 mutant to hydroxyurea, but the WRN helicase did not. We discussed differential roles of BLM and WRN helicases in human cells. BLM- and WRN-bearing yeasts provide new useful models to investigate human BS and WS diseases.

Base Sequence↗
PubMed1998

Effects of lysophosphatidic acid on proliferation of stellate cells and hepatocytes in culture.

Lysophosphatidic acid (LPA) is a growth factor-like mediator for fibroblasts or smooth muscle cells produced and released by activated platelets. Platelet activation occurs with hepatic necrosis and subsequent liver regeneration and fibrosis. In the fibrosis, hepatic stellate cells proliferate with phenotypic transformation to myofibroblasts. Thus, effects of LPA on proliferation of hepatocytes and stellate cells were investigated. In cultured rat stellate cells, LPA increased DNA synthesis with enhanced MAP kinase activity. Pertussis toxin (PTX) attenuated this mitogenic action. In contrast, LPA decreased DNA synthesis by cultured rat hepatocytes induced by hepatocyte growth factor (HGF) or epidermal growth factor (EGF) without affecting protein synthesis. Enhanced MAP kinase activity by HGF or EGF was not changed by LPA. This anti-mitogenic action was attenuated by PTX. TGFbeta level in the medium was less than the level effective for inhibiting the DNA synthesis in the presence of LPA. Our results suggest that LPA might affect proliferation of hepatocytes and stellate cells in liver diseases complicating platelet activation.

Animals↗
PubMed1998

Increased risk of hepatoblastoma among immature children with a lower birth weight.

Hepatoblastomas among children with very low birth weights have significantly increased recently, according to the data from the Japan Children's Cancer Registry for the years 1985-1993. We then analyzed more Registry data for 1969-1994 to clarify the possible relationship between low birth weight and hepatoblastoma. The percentage of low birth weights was compared between 543 hepatoblastoma children in the Registry and all live births in Japan in four successive periods during the 26 years from 1969 to 1994, in relation to the given birth year. The percentage of children with birth weights of 1500-1999 g among hepatoblastomas was higher, at 2.94-1.60%, than that among all live births in each of the four periods (0.79-0.92%), and the percentage of children with birth weights of 2000-2499 g was slightly higher. The percentage of children with birth weights of <1500 g and, especially, <1000 g, has increased rapidly among children born after 1988 (1.60 and 6.40%, respectively), when most very low birth weight infants began to survive. Compared with children with a birth weight of 2500 g or more, the relative risks of hepatoblastoma among children with birth weights of <1000, 1000-1499, 1500-1999, and 2000-2499 g were 15.64 (P < 0.001), 2.53 (P = 0.129), 2.71 (P = 0.001), and 1.21 (P = 0.381), respectively, suggesting the lower the birth weight, the higher the risk of hepatoblastoma. There was no association between hepatoblastomas with a low birth weight and either age at diagnosis or congenital malformations or light-for-date weight. The risk of hepatoblastoma for low birth weight children may be inherently high, especially for lower birth weights, and the recent rapid increase may be a result of an increase in the number of more immature infants with a more sensitive liver and also more frequent exposure to risk factors related to perinatal treatment.

Adolescent↗
PubMed1998

Estrogen-induced tumorigenesis in the pituitary gland of TGF-beta(+/-) knockout mice.

Transforming growth factor (TGF)-beta receptor type II gene (Tgfbr2) knockout and wild type mice underwent chronic estrogen exposure using estradiol pellets. Histological examination of the pituitary glands found 38 adenomas in 14 Tgfbr2(+/-) mice but only one tumor in ten wild type mice. Pituitary tumorigenesis is greatly accelerated in Tgfbr2(+/-) mice by estrogen treatment.

Adenoma↗
PubMed1998

Crystal structures of B-DNA with incorporated 2'-deoxy-2'-fluoro-arabino-furanosyl thymines: implications of conformational preorganization for duplex stability.

The fundamental conformational states of right-handed double helical DNA, the A- and B-forms, are associated with distinct puckers of the sugar moieties. The furanose conformation itself is affected by the steric and electronic nature of the ring substituents. For example, a strongly electronegative substituent at the C2' position, such as in the 2'-deoxy-2'-fluoro ribo furanosyl analogue, will drive the conformational equilibrium towards the C3'- endo type (north). Conversely, the 2'-deoxy-2'-fluoro arabino furanosyl modification with opposite stereochemistry at C2' appears to have a preference for a C2'- endo type pucker (south). Incorporation of 2'-fluoroarabinofuranosyl thymines was previously shown to enhance the thermodynamic stability of B-DNA duplexes. We have determined the crystal structures of the B-DNA dodecamer duplexes [d(CGCGAASSCGCG)]2and [d(CGCGAASTCGCG)]2with incorporated 2'-deoxy-2'-fluoroarabinofuranosyl thymines S (south) at 1.55 A resolution. In the crystal structures, all S residues adopt an O4'- endo conformation (east), well compatible with an overall B-form duplex geometry. In addition to the increased rigidity of S nucleosides, a clathrate-like ordered water structure around the 2'-fluorines may account for the observed larger thermodynamic stability of DNA duplexes containing 2'-deoxy-2'-fluoroarabino thymidines.

Arabinofuranosyluracil↗
PubMed1998

Experiences of 23 patients > or = 90 years of age treated with radiation therapy.

PURPOSE: To present 23 patients > or = 90 years old treated with radiotherapy, and to retrospectively evaluate the results of radiotherapy and tolerance in these patients. METHODS AND MATERIALS: The clinical records of 27 patients over 90 years of age who were treated with radiotherapy at the Department of Radiology, Shinshu University Hospital, and eight affiliated general hospitals from 1990 until 1995 were reviewed. The strategy of radiotherapy was individually planned depending on the stage of the disease and performance status (PS) of the patient; however, it was not modified, based solely on chronologic age. The overall survival rate and disease-free survival rate were determined using the Kaplan-Meier method. The Radiation Therapy Oncology Group scoring criteria of acute and late reactions of radiation therapy were used. RESULTS: This group of patients accounted for 0.37% of all patients treated with radiotherapy in these hospitals. Of these, 23 patients in whom cancer was pathologically confirmed and whose follow-up data were available for retrospective analysis were included in the final evaluation of data. The age of the 23 patients ranged from 90 to 96 years (median 93). Tumor was untreated and in the early stage in five patients, locoregionally advanced in 13, recurrent in four, and systemic in one. Definitive radiation therapy was administered in 12 patients (13 sites), preoperative intent in one, and palliative intent in 10. The period of observation ranged from 2.5 to 6 years (median 18 months). Seven patients were alive for 15-67 months. Fourteen patients died because of intercurrent diseases or senility associated with active cancer, and two because of senility without evidence of cancer. The overall and relapse-free survival rates were 65% and 30% at 1 year and 30% and 21% at 2 years, respectively. Definitive radiation therapy was completed in 13 of 13 patients (100%), and local control was attained in 9 of 13 patients at 6 months (62%). Palliative radiation therapy was completed as intended in 7 of 11 (64%), and effects of palliation were observed in 9 of 11 patients (81%). Acute dermatitis, mucositis, pharyngitis, esophagitis, and cystitis of grade 2-3 related to the definitive radiation therapy were tolerable for the patients with good PS. It took 3-7 weeks (median 5) for acute moist desquamation of six lesions of skin cancer to heal. Depending on the radiation doses, grade 1-2 atrophy of skin and telangiectasia were documented for eight patients followed up for more than 1 year. A brief description of representative case is presented. CONCLUSION: Patients older than 90 years with good PS may tolerate the acute effects of radiotherapy administered according to conventional fractionation schedules. Definitive radiation therapy should be considered, when applicable, even for patients older than 90 years.

Aged↗
PubMed1998

The effect of two antipodal fluorine-induced sugar puckers on the conformation and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)]2.

UV thermal melting studies, CD and NMR spectroscopies were employed to assess the contribution of antipodal sugar conformations on the stability of the canonical B-DNA conformation of the Dickerson-Drew dodecamer duplex [[d(CGCGAATTCGCG)]2, (ODN 1)]. Different oligodeoxynucleotide versions of ODN 1 were synthesized with modified thymidine units favoring distinct sugar conformations by using a 3'- endo (north) 2'-fluoro-2'-deoxyribofuranosyl thymine (1) or a 2'- endo (south) 2'-fluoro-2'-deoxyarabinofuranosyl thymine (2). The results showed that two south thymidines greatly stabilized the double helix, whereas two north thymidines destabilized it by inducing a more A-like conformation in the middle of the duplex. Use of combinations of north and south thymidine conformers in the same oligo destabilized the double helix even further, but without inducing a conformational change. The critical length for establishing a detectable A-like conformation in the middle of a B-DNA ODN appears to be 4 bp. Our results suggest that manipulation of the conformation of DNA in a sequence-independent manner is possible.

DNA↗
PubMed1998

Development of unfavorable hepatoblastoma in children of very low birth weight: results of a surgical and pathologic review.

BACKGROUND: The incidence of hepatoblastoma in children of very low birth weight (< 1500 g) is increasing in Japan. The authors reviewed surgical and pathologic aspects of the tumor to clarify the characteristics of the patients. METHODS: Fifteen patients (9 boys and 6 girls) who were diagnosed between the ages of 6-77 months (median, 16 months) were identified from the data in the Japan Children's Cancer Registry and the data base of medical journals. The patients' birth weights ranged from 560-1380 g (median, 826 g) and the gestational age ranged from 23-33 weeks (median, 25 weeks). The medical records of all patients were reviewed and the patient's stage of disease according to the classification of the Japanese Society of Pediatric Surgeons, treatment, and outcome were analyzed. RESULTS: Ten tumors (67%) were classified as Stage II or IIIA and 5 (33%) were classified as Stage IIIB or IV. There was a significant correlation between the gestational age and tumor stage (correlation coefficient - 0.6851; P = 0.0048). The gestational age of the 5 patients with Stage IIIB or IV tumors was 23-25 weeks (median, 24 weeks), whereas it was 25-33 weeks (median, 27.5 weeks) for the 10 patients with Stage II or IIIA tumors (P = 0.0036). Birth weight ranged from 560-826 g (median, 734 g) in Stage IIIB and IV patients, which was significantly lower than that in Stage II and IIIA patients (range, 607-1380 g, median, 909 g; P = 0.0500). Complete tumor resection was achieved in 7 patients (47%). The actuarial 2-year survival of all patients was 0.42, and the 2-year survival of patients who underwent complete tumor resection was 0.69, which was significantly better than the 2-year survival of those who underwent incomplete resection (0.17; P = 0.0211). The 2-year survival of the patients with tumors of well differentiated histology was 0.60, which also was significantly better than the 2-year survival of those with tumors of poorly differentiated histology (0.19; P = 0.0453). CONCLUSIONS: These results indicate that children of very low birth weight (< 1500 g) are at high risk of developing advanced hepatoblastomas and that hepatoblastoma with unfavorable biologic behavior develops in children who are extremely premature at birth. These new findings suggest the presence of etiologic factors relevant to the patient's immaturity and the development of unfavorable hepatoblastoma.

Child↗