PubMed HealthSearch

Biomedical subjects

T Furukawa

Publications and source records attributed to T Furukawa.

At least 19 recordsLinked to original sources

[MR imaging of stereotactic thalamotomy using radiofrequency methods].

Sixty-eight stereotactic radiofrequency (rf) thalamic lesions in 57 patients with movement disorders were evaluated by magnetic resonance (MR) imaging. Postoperative periods ranged from 5 days to 4 years and 9 months. All 68 rf lesions were clearly detected on T2-weighted images (T2WI). Changes in signal intensity on T2WI were classified into five patterns, as follows: Pattern I: lesions with three concentric zones consisting of an inner hypointense, middle hyperintense and outer hypointense zone (31 lesions); Pattern II: lesions consisting of an inner hypointense and outer hyperintense zone (4 lesions); Pattern III: lesions consisting of an inner hyperintense and outer hypointense zone (27 lesion); Pattern IV: lesions of a hyperintense area alone (2 lesions); Pattern V: lesions of a hypointense area alone (4 lesions). The outer hypointense rim in Patterns I and III is thought to represent hemosiderin deposition. The abnormal signal intensity on T2WI caused by rf ranged from 2 to 12 mm in diameter, and lesions in the late phase were smaller than lesions in the early phase.

Adolescent

The mucus-hypersecreting tumor of the pancreas. Development and extension visualized by three-dimensional computerized mapping.

BACKGROUND: Mucus-hypersecreting tumor of the pancreas appears as dilated ducts and cystic spaces filled with mucus. To determine where such tumors arise and how they extend, computer-aided three-dimensional reconstruction was done of the ductal system. This also was used to visualize the spatial relationships among epithelial hyperplasia, dysplasia, and carcinoma in situ (CIS). METHODS: Surgically removed pancreases were studied from 12 patients with mucus-hypersecreting tumors. The specimens were fixed in buffered formaldehyde solution 10%, embedded in paraffin and semiserially sectioned at 3 microns at an interval of 60 microns. The ductal contours were differentiated among ducts lined by ordinary epithelia, hyperplastic epithelia, dysplastic cells, or CIS and were inputted into a computer system that integrated a three-dimensional image of ducts in the display. RESULTS AND CONCLUSIONS: (1) The tumors arose in the main pancreatic duct or its subbranches, and the cysts corresponded to segments expanded by the superficial growth of tumor cells; (2) areas of CIS arose in zones of preceding dysplasia, suggesting a dysplasia-carcinoma sequence; and (3) dysplastic or cancerous cells often extended intraductally over the dilated segments of ducts.

Aged

Ultrastructural and ultracytochemical differences between megakaryoblastic leukemia in children and adults. Analysis of 49 patients.

BACKGROUND: Acute megakaryoblastic leukemia (AMKL) has two peaks in distribution of incidence (in adults and children 1 to 2 years of age) and is frequently seen in children with Down syndrome. The current study was undertaken to disclose whether there were any differences between these groups. METHODS: Electron microscopic and ultrastructural cytochemical features of 49 children and adults with a AMKL or chronic myelogenous leukemia (CML) in megakaryoblastic crisis were compared. RESULTS: Blast cells from children with AMKL, including those with and without Down syndrome, had immature features lacking typical alpha granules and a demarcation membrane system (DMS). However, blast cells from patients with AMKL with Down syndrome had more theta, electron-lucent, and basophil-like granules, suggesting that the blast cells had more potential to differentiate into other cell lines than megakaryocytes. The AMKL blast cells of adult patients showed a higher percentage of platelet peroxidase (PPO) positivity than other subgroups, and they occasionally contained typical alpha granules and DMS. This indicated that the blast cells of adults with AMKL were more mature than those of children and CML in megakaryoblastic crisis. CONCLUSIONS: By electron microscopic analysis, leukemic megakaryoblasts differed between children with AMKL with and without Down syndrome, adults with AMKL, and patients with CML in megakaryoblastic crisis.

Acid Phosphatase

Effect of a dihydropyridine analogue, 2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo- 1,3,2-dioxaphosphorinan-2-yl)-1-(2-morpholinoethyl)-4-(3-nitrophenyl)-3 -pyridinecarboxylate on reversing in vivo resistance of tumor cells to adriamycin.

A newly synthesized dihydropyridine analogue, 2-[benzyl(phenyl)-amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2-yl)-1- (2-morpholinoethyl)-4-(3-nitrophenyl)-3-pyridinecarboxylate (PAK-200), at 5 microM inhibited the efflux of [3H]vincristine from KB-C2 cells and increased the accumulation of [3H]vincristine in KB-C2 cells to a level similar to that in KB-3-1 cells. PAK-200 inhibited the photoaffinity labeling of P-glycoprotein in KB-C2 membranes by [3H]azidopine. At 5 microM, PAK-200 enhanced the cytotoxic effect of Adriamycin on drug-sensitive KB-3-1 cells, multidrug-resistant KB-8-5 cells, and two human colorectal carcinoma tumor lines, COK-28LN and COK-36LN, by factors of 2, 5, 2, and 3 times, respectively. The calcium antagonistic activity of PAK-200 was about 1000 and 5 times lower than that of another dihydropyridine analogue, nicardipine, and of verapamil, respectively. PAK-200 in combination with Adriamycin completely suppressed the growth of KB-3-1 and COK-36LN and partially suppressed the growth of KB-8-5 but had no significant effect on COK-28LN cells xenografted in nude mice. The level of MDR1 expression of COK-36LN was about 3 times higher than that of COK-28LN, but lower than that of KB-8-5 cells. These results suggest that the interaction of PAK-200 with P-glycoprotein may be partly correlated with the enhancement of the antitumor effect of Adriamycin on xenografted KB-8-5 and COK-36LN cells in nude mice.

Animals

The Drosophila homolog of the immunoglobulin recombination signal-binding protein regulates peripheral nervous system development.

The J kappa RBP binds to the immunoglobulin recombination signal sequence flanking the kappa-type J segment. We previously isolated the highly conserved homolog of the J kappa RBP gene from D. melanogaster, which is not thought to have immunoglobulin molecules. Using many deficiency mutants and in situ hybridization, we mapped the Drosophila J kappa RBP gene in a region containing two recessive lethal mutations, i.e., br26 and br7, which shows the dominant Suppressor of Hairless (Su(H)) phenotype in heterozygotes. All six Su(H) alleles analyzed at the DNA level contained mutations in the Drosophila J kappa RBP gene. Since the Su(H) mutation affects peripheral nervous system development, the Drosophila J kappa RBP gene product is involved in gene regulation of peripheral nervous system development. The results also imply that the immunoglobulin recombination signal sequence and the target sequence of the Drosophila J kappa RBP protein might have a common evolutionary origin.

Alleles

High in vitro-in vivo correlation of drug response using sponge-gel-supported three-dimensional histoculture and the MTT end point.

The in vitro sponge-gel-supported three-dimensional histoculture chemosensitivity assay (Hoffman assay) allows the in vivo-like culture of human tumors. In this study, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) end point was applied to the Hoffman assay in an attempt to increase in vitro-in vivo correlation. The chemosensitivities of 16 human tumor lines were determined in vitro by the histoculture assay, and retrospectively correlated to their in vivo chemosensitivity as xenografts in nude mice. The in vitro test was considered to be positive if tumor-cell MTT reduction activity was lowered by more than 50%. The cutoff drug concentrations to determine sensitivity in vitro were determined for mitomycin C, doxorubicin, 5-fluorouracil and cisplatin. Using these cutoff drug concentrations in vitro we found, as a function of time of exposure, a strong correlation between serum drug concentrations found in nude mice given maximum tolerated doses and drug concentrations found in the histoculture media in vitro, thereby establishing a relationship between the amounts of drugs to which tumors were exposed in vivo and in vitro. The overall correlation rate of the efficacy results of the drug-response assay to in vivo chemosensitivities was 89.8%, with 90.0% true-positive and 89.7% true-negative rates, 81.7% sensitivity and 94.6% specificity, thereby indicating potential clinical use for tumor histoculture with the MTT end point.

Animals

Angiogenic factor.

Explore the source record for details and available documents.

Escherichia coli

Increased drug resistance of cultured human cancer cell lines in three-dimensional cellular growth assay using collagen gel matrix.

We have conducted a three-dimensional cellular growth assay using collagen gel matrix with an endpoint of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay, on four human gastric and colonic cancer cell lines. Three-dimensionally growing cells in collagen gel matrix were 2- to 180-fold more resistant to mitomycin C, doxorubicin, 5-fluorouracil, and cisplatin than those in monolayer culture, and these resistances were increased further when the cells increased their three-dimensionality. Furthermore, the influence of fibroblasts in the collagen gel matrix on the chemosensitivity of cancer cells was less than that in monolayer culture. Since this new assay using collagen gel matrix with an endpoint of the MTT assay was able to detect the increase of drug resistance of human cancer cell lines by three-dimensional cellular growth using a simple and convenient procedure, it was considered to be more useful than conventional monolayer cultures for evaluating the chemosensitivity of cancer cells.

Adenocarcinoma

Targeting cancer chemotherapy using a monoclonal antibody (NCC-LU-243) conjugated with mitomycin C.

Two kinds of immunoconjugate (T-3M and T-11M) of murine monoclonal antibody with mitomycin C (MMC) were developed using spacers containing a disulfide (T-3M) or thiocarbamate (T-11M) bond. A murine monoclonal antibody (NCC-LU-243) raised against a human small cell lung carcinoma cell line, Lu-24, in nude mice, is an IgG2a monoclonal antibody that recognizes a 145-kDa protein on the cell surface membrane. T-3M and T-11M showed affinity for the LU-243 antigen-positive H-69 cell line but not for the antigen-negative Lu-65 cell line in vitro. In the in vitro MTT assay, the order of efficacy of these compounds was T-11M > T-3M > MMC against antigen positive H-69 and T-11M = MMC > T-3M against antigen-negative K562. When antigen-positive H-69 was transplanted into nude mice for in vivo assay, the maximum tolerated dose of T-3M was twice as high than that of the parent compound MMC. Furthermore, T-3M showed higher antitumor activity against antigen-positive H-69 than MMC conjugated with a non-specific rabbit IgG in vivo. When the maximum tolerated doses of T-3M and MMC were administered to H-69-bearing nude mice, the effect of T-3M was superior to that of MMC, whereas no differences were observed between the antitumor activity of T-3M and MMC against antigen- negative MX-1, a human breast carcinoma. These two immunoconjugates of monoclonal antibody with mitomycin C are thought to be useful for targeting cancer chemotherapy against human small cell lung carcinomas.

Animals

Pseudoenhancement of intervertebral disc herniation.

Two patients with intervertebral disc herniation appeared to demonstrate abnormally diffuse and intense enhancement of the disc after intravenous administration of gadolinium-DTPA for MRI. Surgery disclosed a dilated epidural venous plexus in one and vascular granulation tissue in the other, associated with the herniated disc material. The mechanism of this "pseudoenhancement" of the disc appears to be a partial volume effect of disc material and the adjacent veins or granulation tissue. Pseudoenhancement of a herniated disc should be included in the differential diagnosis of a diffusely enhancing epidural mass.

Aged

MR imaging and angiography of cerebral venous angiomas associated with brain tumors.

MR study of 6 patients with concurrent venous angioma and brain tumor revealed that in 2 of the 6 cases, the draining vein of the venous angioma was located near to the tumor and was displaced by the tumor. Two of the 6 venous angiomas were too small to visualize prior to contrast enhancement, but could be detected following administration of Gd-DTPA. Angiography was required for definitive diagnosis of the venous angiomas. When a venous angioma is suspected or is detected incidentally, especially when very near a brain tumor, angiography should be considered before performing surgery to avoid surgical complications. Otherwise, ligation of the vein draining the venous angioma may lead to venous infarction.

Adolescent

A simple elimination of clonogenic tumor cells from human bone marrow in vitro by heat: its application to autologous bone marrow transplantation for B-cell lymphoma.

The application of hyperthermia to the treatment of neoplastic disease has focused on solid tumors. Since the hyperthermic sensitivity of human B-cell lymphoma cells is not known, we have examined the effect of hyperthermia on the growth of B-cell lymphoma cell lines (Raji and Daudi) in vitro to evaluate the ability to purge tumor cells from normal bone marrow by heat, utilizing a limiting-dilution assay to measure log depletion of tumor cells in a 20-fold excess of normal bone marrow. When exposed at 42 degrees C and 43 degrees C for 120 min, both clonogenic Raji and Daudi cells were dramatically decreased (a 4- to 6-log reduction) with exposure time, while leaving over half of the normal granulocyte-macrophage progenitor cells surviving at 42 degrees C and 10% at 43 degrees C. This high level of lymphoma-cell depletion by heat correlated with that obtained in immunologic and pharmacologic studies. These results suggest that in vitro hyperthermia might be applied effectively for the elimination of residual lymphoma cells in autologous marrow grafts before autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma.

Bone Marrow

Ultrastructural study of the glomerular slit diaphragm in fresh unfixed kidneys by a quick-freezing method.

In normal kidneys fixed by perfusion with tannic acid and glutaraldehyde, glomerular slit diaphragms have been reported to consist of highly ordered and isoporous substructures with a zipper-like configuration. We have re-evaluated the ultrastructure of fixed or unfixed glomeruli using quick-freezing and deep-etching (QF-DE) and freeze-substitution (QF-FS) methods. In the fixed slit diaphragms, zipper-like substructures were often observed by the QF-DE method. In contrast, in fresh unfixed glomeruli the slit diaphragms mainly consisted of non-porous substructures. The slit diaphragms were more widely opened in the fixed glomeruli, as examined by the QF-FS method. These results suggest that the foot processes shrink during tissue preparation by conventional methods with chemical fixatives, and that the broadening of slit diaphragms and zipper-like substructures are formed by the pulling apart of adjacent foot processes due to shrinkage.

Animals

Ribosomal protein P2, a novel iron-binding protein.

We examined the properties of a new iron-binding protein purified previously from rat liver (T. Furukawa, S. Taketani, H. Kohno, and R. Tokunaga, 1991, Biochem. Biophys. Res. Commun. 181, 409-415). The protein was digested with trypsin and the peptides were analyzed by reverse-phase high-performance liquid chromatography. The partial amino acid sequences of the tryptic peptides coincided with that of rat ribosomal protein P2. Immunoblot analysis and iron-binding assay confirmed that the iron-binding protein and ribosomal protein P2 are identical. Then the iron binding ability of ribosomal protein P2 was examined in rat hepatoma H4IIEC3 cells incubated with radioactive iron. When immunoprecipitation with anti-iron-binding protein serum was performed using cells incubated with 59Fe-citrate, about 4% of the 59Fe radioactivity in cells was associated with the iron-binding protein through 30 to 90 min of incubation. About 1.5% of radioactive iron in cells incubated with 59Fe-transferrin was found in immunoprecipitates with anti-iron-binding protein serum during 1 to 5 h of incubation, and 4 to 7% of the radioactivity was found in immunoprecipitates with a monoclonal antibody against ribosomal P proteins in the same incubation. These results demonstrate that ribosomal proteins P2 binds iron taken up by the cells.

Amino Acid Sequence

Inhibitory effects of endothelin-1 and endothelin-3 on prolactin release: possible involvement of endogenous endothelin isopeptides in the rat anterior pituitary.

Spontaneous prolactin release from the isolated rat anterior pituitary was inhibited by endothelin-1 in a dose-dependent manner (10(-8)-10(-6) M). Endothelin-3 also inhibited spontaneous prolactin release with an almost identical dose-response relationship as endothelin-1. These inhibitory effects were unaffected by application of a dopamine D2-receptor antagonist, YM-09151-2 (10(-7) M). Rat anterior and posterior pituitary glands were abundant in both endothelin-1 and endothelin-3, as compared with other regions of the brain. The present results suggest that endogenous endothelin-1 and endothelin-3 in the anterior and posterior pituitary are involved in the inhibitory regulation of prolactin secretion as autocrine or paracrine factors.

Analysis of Variance

Iron deprivation decreases ribonucleotide reductase activity and DNA synthesis.

The effects of the iron-chelator, desferrioxamine, and monoclonal antibodies against transferrin receptors on DNA synthesis and ribonucleotide reductase activity were examined in human leukemia K562 cells. Treatment of the cells with desferrioxamine resulted in decreases of ribonucleotide reductase activity, DNA synthesis, and cell growth. Exposure of the cells to anti-transferrin receptor antibody, 42/6, which blocks iron supplement into cells caused decreases of ribonucleotide reductase activity and DNA synthesis, in a parallel fashion. Decreases of ribonucleotide reductase activity and DNA synthesis by 42/6 were restored by the addition of ferric nitriloacetate. These results indicate that ribonucleotide reductase activity is dependent on the iron-supply and also regulates cell proliferation.

Antibodies, Monoclonal

Role of adrenergic neuronal activity in the yawning induced by tacrine and NIK-247 in rats.

The present experiments were performed to investigate the potential role of central adrenergic neurons in regulating occurrence of yawning in rats. Intraperitoneal injection of tacrine (THA) or 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)-quinoline monohydrate HCl (NIK-247), cholinesterase inhibitors, induced yawning, which was markedly increased by pretreatment with the beta-adrenoceptor antagonist, pindolol. The yawning evoked by tacrine or NIK-247 given alone or in combination with pindolol was inhibited by pretreatment with scopolamine but not by mecamylamine or spiperone. Treatment with tacrine or NIK-247 increased acetylcholine content of the striatum, but this effect was not enhanced by pindolol, which per se did not affect basal acetylcholine content. Moreover, pretreatment with the central adrenaline synthesis inhibitors, (+-)-2,3-dichloro-alpha-methylbenzylamine HCl (LY-78335) and 2-cyclooctyl-2-hydroxyethylamine HCl (UK-1187A), increased tacrine-induced yawning. Subcutaneous injection of talipexole (B-HT 920), a dopamine D2 receptor agonist, evoked yawning, which was also increased by pindolol, LY-78335, and UK-1187A. These receptors antagonists and synthesis inhibitors per se did not cause yawning responses. The results suggest that the beta-adrenoceptor blockade and the inhibition of adrenaline synthesis facilitate the occurrence of yawning induced by cholinergic and dopaminergic agonists, and thus the central adrenergic neuronal systems may be implicated in the regulation of yawning responses.

Acetylcholine