Absence of a first-order metamagnetic transition in CeRu2Si2.
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Journal Article↗
Biomedical subjects
T Sakakibara
Publications and source records attributed to T Sakakibara.
The anti-proliferative effect of proliferating cell nuclear antigen-specific antisense oligonucleotides on human gastric cancer cell lines.
The proliferating cell nuclear antigen (PCNA) is a nuclear protein that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10-40 microM dose-dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer.
Base Sequence↗
Kissing aneurysms of distal anterior cerebral arteries demonstrated by magnetic resonance angiography.
BACKGROUND Multiple aneurysms, associated with distal anterior cerebral artery (ACA) aneurysm, are not rare; therefore, it is important to examine multiplicity of the aneurysms preoperatively. CASE REPORT A case of ruptured distal ACA aneurysm, associated with another one in a mirror position, is reported. A 43-year-old woman suffered subarachnoid hemorrhage. Conventional angiography demonstrated a saccular aneurysm on the bifurcation of the right or left distal ACA; however, magnetic resonance angiography (MRA) revealed two mirror-image aneurysms on both bifurcations. CONCLUSION MRA was useful for preoperative diagnosis of kissing aneurysms on distal ACAs.
Adult↗
Site-specific implantation in the milky spots of malignant cells in peritoneal dissemination: immunohistochemical observation in mice inoculated intraperitoneally with bromodeoxyuridine-labelled cells.
To investigate the site-specific implantation of cancer cells in peritoneal dissemination, we inoculated CDF1 mice intraperitoneally with mouse P388 leukaemia cells labelled with bromodeoxyuridine (BrdU) and then observed immunohistochemically the distribution of the cells in the greater omentum taken from the mice using an anti-BrdU antibody. We found the BrdU-labelled cells infiltrating selectively into the milky spots in the omentum. Furthermore, we intraperitoneally inoculated the BrdU-labelled P388 cells at 10(5), 10(6) and 10(7) cells per mouse into three groups of ten CDF1 mice and then quantified the distribution of the BrdU-labelled cells by counting the number of the labelled cells per unit area at each milky spot and non-milky spot site in the omentum. Inoculations of 10(5), 10(6) and 10(7) BrdU-labelled P388 cells per mouse resulted in 15.8 +/- 13.3, 120 +/- 46.5 and 504 +/- 208 cells mm-2 respectively in the milky spot sites and 9.14 x 10(-3) +/- 1.58 x 10(-2), 1.14 x 10(-1) +/- 7.82 x 10(-2) and 7.07 x 10(-1) +/- 5.98 x 10(-1) cells mm-2 respectively in the non-milky spot sites. The ratios of the mean labelled cell numbers in the milky spot sites vs those in the non-milky spot sites were 1728:1, 1049:1 and 713:1 respectively. In all cases, there were statistically significant differences in the number of BrdU-labelled cells mm-2 between milky spot sites and non-milky spot sites. However, the ratios decreased as the numbers of inoculated cells increased. In addition, we inoculated C57/BL mice intraperitoneally with B-16 PC melanoma cells, which were easily differentiated from the other cells by the intrinsic black melanin, and examined the distribution of the cells macro- and microscopically. The B-16 PC melanoma cells were also found to be infiltrating preferentially into the milky spots in the omentum. These results suggest that cancer cells seeded intraperitoneally specifically infiltrate the milky spots in the early stages of peritoneal dissemination.
Animals↗
Therapeutic effects of the angiogenesis inhibitor TNP-470 against carcinomatous peritonitis in mice.
The therapeutic effects of the new anti-angiogenesis factor TNP-470 were examined against carcinomatous peritonitis in mice. In the first experiment using carcinomatous peritonitis caused by i.p. inoculation of 10(6) M5076 tumor cells, TNP-470 solution was injected i.p. in a bolus of 50 mg/kg body weight into two groups of 10 mice either 1 or 8 days after the i.p. inoculation. The administration of TNP-470 on day 1 extended the survival time of the mice compared with 10 control mice receiving no treatment, whereas TNP-470 given on day 8 did not affect the survival time. In the next experiment on the M5076 tumor, TNP-470 solutions at 100 or 300 mg/kg were injected i.p. in a bolus into two groups of 20 mice 1 day after the inoculation 10(6) tumor cells, respectively. The administration of TNP-470 at 100 mg/kg also had an inhibitory effect. However, TNP-470 at 300 mg/kg caused toxic death in half of the mice. Next, we examined the effects of TNP-470 on another type of carcinomatous peritonitis model, which was caused by i.p. inoculation of 10(6) B16 melanoma cells. In this experiment, TNP-470 solutions in a bolus of 150 mg/kg were injected i.p. into six groups of 10 mice each on day 1 only (group 1), on days 1 and 4 (group 2), on days 1, 4 and 7 (group 3), on day 8 only (group 4), on days 8 and 11 (group 5), or on days 8, 11 and 14 (group 6), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Inhibition of colon cancer cell proliferation by antisense oligonucleotides targeting the messenger RNA of the Ki-ras gene.
Point mutations that activate the Ki-ras proto-oncogene are present in approximately 50% of human colorectal tumors and the activated Ki-ras gene is considered to play an important role in colorectal cancer cell proliferation. Five different colon cancer cell lines and two kinds of control cell lines were treated with antisense oligonucleotides complementary to the messenger RNA of Ki-ras. Treatment with antisense oligonucleotides at concentrations between 10 and 40 microM significantly and dose-dependently inhibited cell growth, colony formation and Ki-ras protein production of the colon cancer cells with activated Ki-ras, but did not affect the normal cells and colon cancer cells without Ki-ras mutation. These results show that use of synthetic oligonucleotides is an effective way of producing antisense-mediated changes in the behavior of human colon cancer cells with an activated Ki-ras gene.
Antineoplastic Agents↗
Disappearance of arachnoid cysts after head injury.
The mechanism of the disappearance of arachnoid cysts is not fully understood. This article discusses the spontaneous disappearance of these cysts after head injury. Five patients underwent computed tomography and were diagnosed as having a subdural hematoma or effusion associated with arachnoid cysts. In four of the five patients, the cyst decreased in size or disappeared. These cases suggest a possible mechanism by which this type of cyst associated with subdural hematoma or effusion might disappear. For the arachnoid cyst to disappear, the rupture of the cyst wall appears to be essential, and after rupture, subdural effusion must develop around the cyst. As this effusion is absorbed, the fluid in the cyst drains away, after which the cyst becomes smaller and gradually disappears. This hypothesis supports the possibility of a "natural cure" for arachnoid cysts without surgical intervention.
Adolescent↗
Effect of specific binding of high density lipoprotein to eel hepatocytes on their secretion of lipoprotein.
Specific binding of eel serum high-density lipoprotein (HDL) to eel hepatocytes was demonstrated by using a synthesized fluorescent lipophilic dye. HDL binding was inhibited by the addition of unlabeled HDL. The binding of HDL to the hepatocytes was saturated at concentrations over 100 micrograms HDL protein/ml and Kd value was 20 micrograms HDL protein/ml. A fluorescent photomicrograph of the cultured eel hepatocytes which were incubated with the dye showed the bright, circumferential plasma membranes stained with the dye. 125I-HDL was incorporated into the acid insoluble- and soluble-fractions of the cultured hepatocytes during incubation at 28 degrees C for 1 h. There are three remarkable characteristics of the effect of HDL on the cultured hepatocytes. One is that the addition of HDL to the hepatocytes induced the efflux of cholesterol, triacylglycerol, and phospholipid from the hepatocytes. The second characteristic is that the efflux of the intracellular lipids was carried out with very-low-density-like or chylomicron-like lipoprotein secreted by the hepatocytes. The third characteristic is that HDL specifically stimulated the synthesis of the lipoprotein and had no effect on the synthesis of intracellular proteins and the secreted proteins except for the lipoprotein.
Anguilla↗
CJ-12,371 and CJ-12,372, two novel DNA gyrase inhibitors. Fermentation,isolation, structural elucidation and biological activities.
A fermentation broth of an unidentified fungus (N983-46) was found to produce DNA gyrase inhibitors, CJ-12,371 (1) and CJ-12,372 (2). Following isolation by solvent extraction and silica gel and ODS (reverse phase) chromatographies, the structures were determined to be novel spiro-ketal compounds with S-configuration at position C-1. CJ-12,371 and CJ-12,372 inhibit both DNA supercoiling and relaxation mediated by Escherichia coli DNA gyrase. The interaction of these compounds with DNA gyrase appears to be novel in that the compounds inhibit supercoiling and relaxation without blocking religation; thus, no cleavage intermediate of double strand DNA is observed. Both compounds have antibacterial activity against several species of pathogenic Gram-positive bacteria, with MICs between 25 and 100 micrograms/ml. These results suggest that the antibacterial potency of CJ-12,371 and CJ-12,372 is attributed to the inhibition of DNA gyrase. However, the compounds did not inhibit DNA gyrase selectively, as they also inhibited eukaryotic topoisomerase II-mediated relaxation. Semi-synthetic modifications to the dihydroxy motif in CJ-12,371 altered both gyrase- and topoisomerase II-inhibitory activities, but did not enhance selectivity.
Anti-Bacterial Agents↗
Generation of novel rapamycin structures by microbial manipulations.
A new rapamycin producing culture was isolated and designated as Actinoplanes sp. N902-109. The addition of a cytochrome P-450 inhibitor and precursor feeding using this culture, and biotransformation approaches generated new rapamycin analogs with modifications at C-4, C-9, C-16, C-27, C-28 and/or C-39. The immunosuppressive activity of the resulting analogs was established in the mixed lymphocyte reaction assay.
Actinomycetales↗
[Therapy of carcinomatous peritonitis by the angiogenesis inhibitor TNP-470 in mice: analysis of timing and doses for intraperitoneal administration].
In order to perform therapy for carcinomatous peritonitis by a new angiogenesis inhibitor, TNP-470, we investigated the effective timing and the optimal doses for intraperitoneal administration using two mice models. In both carcinomatous peritonitis models caused by M 5076 tumor and B 16 melanoma, the early administration of TNP-470 within one week after tumor inoculation extended the survival times of the mice receiving the drugs, whereas the administration of TNP-470 one week or later after inoculation did not affect the survival time. However, there were significant differences in the effective therapeutic doses of TNP-470 between the two models. It is important to select the best timing and doses for intraperitoneal administration of TNP-470 based on the state of angiogenesis and the sensitivity of the tumor tissues to TNP-470.
Animals↗
[Trial of a treatment for lymph node metastases in patients with breast cancer using aclarubicin bound to activated carbon particles].
A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine activated carbon particles, was developed for the treatment of lymph node metastases in patients with breast cancer. In a mice experimental model, ACR-CH had superior therapeutic effects on lymph node metastases compared to the same dose of ACR aqueous solution. In clinical trials, patients with breast cancer received a local injection of 10 mg/person of ACR in the form of ACR-CH or ACR aqueous solution just before mastectomy. In the regional lymph nodes removed by the operation, the ACR concentration of 40.7 micrograms/g in patients given ACR-CH was higher than the 25.1 micrograms/g in patients given ACR aqueous solution, whereas in blood plasma the concentration was higher in patients given ACR aqueous solution than in those given ACR-CH.
Aclarubicin↗
Laparoscopic nephrectomy using a retroperitoneal approach: comparison with a transabdominal approach.
To evaluate the efficacy of the retroperitoneal approach in laparoscopic nephrectomy, our procedures involving laparoscopic nephrectomy using a retroperitoneal approach are described and the clinical results of six patients treated in this way are compared with those of 32 transabdominally nephrectomized patients. Of the six retroperitoneally nephrectomized patients, six kidneys were successfully removed without severe complication, and 28 kidneys were successfully removed in the 32 intraabdominally approached group. Three of the 28 patients had complications requiring open laparotomy. The operating time was 2.7 hours in the 6 retroperitoneal patients and 4.4 hours in the 28 transabdominal patients. Estimated blood loss was 92 ml in the retroperitoneal group and 450 ml in the transabdominal group. The mean postoperative hospital stay was 8 days and 9 days, respectively. These results indicate that the retroperitoneal approach might be preferable in laparoscopic nephrectomy.
Abdomen↗
[Familial amyloidotic polyneuropathy (FAP type I) with late-onset; siblings showing heterogeneity in age of onset].
A 66-year-old man with late-onset FAP type I with Val30-->Met mutation in transthyretin was described. The age of clinical onset was 62 years old. The somatic motor and sensory involvement predominantly distributing in the distal part of the extremities preceded the manifestation of autonomic symptoms. He was diagnosed as having somatic motor and sensory neuropathy. However, 4 years after the onset, autonomic symptoms such as orthostatic hypotension, alternating constipation and diarrhea developed. Sural nerve biopsy and DNA study established the diagnosis of FAP type I. A 77-year-old brother of this patient, also had the type I mutation of transthyretin, but did not show any neurological symptoms or electrophysiological abnormalities, indicating significant discordance to the onset age of clinical phenotypes in this family. As suggested in an experiment on transgenic mice with FAP gene, factors other than FAP gene, possibly an environmental factor, may have been related with the clinical onset of FAP. Both siblings in this family, had FAP type I gene mutations, yet showed a significant discordance to the phenotypic manifestations of FAP. This supports the view that multifactorial background may well influence the clinical onset and progression of this disease.
Age of Onset↗
[Disturbance of hypothalamic-pituitary hormone secretion in familial chorea-acanthocytosis].
An endocrinological study was performed dopaminergic regulation of the hypothalamic-pituitary axis of 3 patients with familial chorea-acanthocytosis (females, 38 to 47 years of age). All 3 patients exhibited low basal levels of triiodo-thyronine (T3), and 2 patients had a slightly elevated baseline plasma prolactin (PRL) level. The patients had a delayed plasma thyroid stimulating hormone (TSH) response and plasma PRL excessive response to thyrotropin releasing hormone (TRH), and a low plasma growth hormone releasing hormone (GRF) response to L-dopa. These TSH, PRL and GRF responses represent a secretion pattern due to a hypothalamic disorder, suggesting impaired regulation of hormone secretion by the dopaminergic system, primarily in the hypothalamus. In addition, an increased growth hormone (GH) response secretion following TRH (paradoxical response) was observed in 2 patients, suggesting that the pituitary was also involved. An oral glucose tolerance test (75g-OGTT) revealed a diabetic pattern in all 3 patients, indicating frequent association with impaired glucose tolerance.
Acanthocytes↗
[A case of subarachnoid hemorrhage with acute subdural hematoma due to head injury: a case report].
Acute intracranial hemorrhages can be caused by cerebrovascular disease or head injury. Diagnostic imaging is in both cases sometimes similar, so it is difficult to make an exact diagnosis. We report a case of acute subdural hematoma due to head injury after loss of consciousness due to an aneurysmal rupture. A 52-year-old male was found out fallen on the floor in a state of unconsciousness and was brought to the nearest hospital. CT scan showed subarachnoid hemorrhage with left acute subdural hematoma and he was transported to our hospital. Angiography revealed a left MCA aneurysm. The next day, a clipping operation was performed but brain contusion was observed in the left frontal lobe. Postoperative CT scan showed contusional hematoma at the left frontal lobe and plain skull X-ray films demonstrated a diastatic fracture of the right lambdoid suture. Acute subdural hematoma due to the rupture of a cerebral aneurysm is sometimes recognized, but the first CT findings are similar to those observed after head injury. When the clinical course of onset is unclear, we must keep in mind that the cause of acute subdural hematoma may be head injury, even if angiography demonstrates abnormal vessels.
Acute Disease↗
Assignment of the true and processed genes for human glycine decarboxylase to 9p23-24 and 4q12.
Southern analysis using a human glycine decarboxylase cDNA probe and genomic DNA preparations from Chinese hamster-human hybridoma cell lines demonstrated that on the segregated human chromosomes, 4 and 9, there are glycine decarboxylase cDNA-related sequences. The finding is confirmatory of the fact that fragments of both the true and processed genes for this protein have been cloned. Since one of four HindIII fragments revealed in the present Southern analysis matched requirements for the property expected from the restriction map reported for the processed gene, this was located on chromosome 4. The three remaining signals were consequently ascribed to fragments from the true gene on chromosome 9. Fluorescence in situ hybridization using the genomic clones assigned the true and processed genes to 9p23-24 and 4q12, respectively.
Amino Acid Oxidoreductases↗
Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin.
Significant activity of phosphatidylinositol 3-kinase (PI 3-kinase) was detected in the membrane fractions, or in the immunoprecipitates prepared with anti-phosphotyrosine antibodies, from rat adipocytes that had been incubated with insulin for 20 min. The PI 3-kinase activity in these preparations as well as in the whole cell lysates of adipocytes not treated with insulin was inhibited by the addition of wortmannin, a fungal metabolite, to the enzyme assay mixture. The inhibition was dependent on the inhibitor concentration with IC50 being less than 10 nM and perfect inhibition at 100 nM. The effect of insulin to induce membrane PI 3-kinase activity was mostly abolished, but its effects to tyrosine-phosphorylate the beta-subunit of the insulin receptor or other cellular substrate proteins including insulin-receptor-substrate-1 were not at all antagonized, by wortmannin added to the cell incubation medium. Insulin stimulation of cellular 2-deoxyglucose uptake and inhibition of isoproterenol-induced lipolysis observable in adipocytes under the same conditions were also antagonized by wortmannin added in the same concentration range as used for the inhibition of insulin-susceptible PI 3-kinase. It is concluded, therefore, that activation of wortmannin-sensitive PI 3-kinase plays a pivotal role in the intracellular signaling pathways arising from the insulin receptor autophosphorylation and leading to certain metabolic responses.
Adipocytes↗