[Design to improve the therapeutic results in A3 esophageal cancer --combined resection and neoadjuvant chemotherapy].
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Chemotherapy, Adjuvant↗
Biomedical subjects
K Toyama
Publications and source records attributed to K Toyama.
[Improvement of respiratory burst by individual neutrophils from a patient with chronic granulomatous disease, type X91- under treatment by granulocyte colony-stimulating factor for multiple liver abscess].
A 20-year-old male with chronic granulomatous disease (CGD) was admitted with multiple liver abscesses. He had already been diagnosed as CGD, type X91-, when he was 10 years old. He was successfully treated with antibiotics and granulocyte colony-stimulating factor (G-CSF) combined with continuous drainage of abscess. Employing flow cytometry, respiratory burst by individual neutrophils was measured using 2', 7'-dichlorofluorescein. The fluorescence intensity in all individual neutrophils from the patient under G-CSF treatment was higher than the one without G-CSF. G-CSF can be one of effective therapies for infection in some patients with CGD such as X91-.
Adult↗
[Use of acetylene rebreathing to measure pulmonary tissue volume in patients undergoing hemodialysis].
Acetylene rebreathing was used to measure pulmonary tissue volume in 10 normal subjects and in 15 patients undergoing hemodialysis. A mixture containing 0.65% acetylene and 10% argon was rebreathed from the end-tidal level, and gas concentrations were measured with a mass spectrometer. Pulmonary tissue volume was computed from the difference between the argon equilibrium concentration and the corrected acetylene concentration, under the assumption that FAr was constant. Measured tissue volumes per unit lung volume (at functional residual capacity) in the normal subjects, before hemodialysis, and after hemodialysis were 0.204 +/- 0.042, 0.334 +/- 0.100, and 0.282 +/- 0.074, respectively. Tissues volumes per unit lung volume were significantly higher in the patients than in the normal subjects, even after hemodialysis. Tissues volumes per unit of lung volume decreased significantly during hemodialysis. Pulmonary blood flows per unit of body surface area of normal subjects, before hemodialysis and after hemodialysis were 3.004 +/- 0.791, 2.790 +/- 1.007, and 2.399 +/- 0.781 (l/min/m2), respectively. These volumes did not differ significantly between normal subjects and patients, and they decreased significantly during hemodialysis. Measured tissue volumes per unit of pulmonary blood flow for normal subjects, before hemodialysis, and after hemodialysis were 0.119 +/- 0.034, 0.167 +/- 0.024, and 0.166 +/- 0.030 (1/1/min), respectively. The values in the patients did not change during hemodialysis, but they were significantly higher than the volumes in the normal subjects.
Acetylene↗
[Chronic myelogenous leukemia received unrelated bone marrow transplantation following surgical resection of cerebral arteriovenous malformation--first case report].
We report a 15-year-old boy with chronic myelogenous leukemia who received unrelated bone marrow transplantation (uBMT) after surgical resection of cerebral arteriovenous malformation (AVM). The incidence of cerebral hemorrhage caused by rupture of cerebral ABM in cases of BMT is uncertain. However, since the risk of rupture of AVM was supposed to increase due to both severe thrombocytopenia after intensive chemotherapy and increased intracranical pressure because of total body irradiation (TBI) as preconditioning therapy for BMT, we have first carried out surgical resection of the cerebral AVM, and subsequently performed uBMT. This resulted in a favorable clinical course without serious complications.
Adolescent↗
[Sleeve lobectomy for tuberculous bronchial stenosis: a case report].
We describe a patient with tuberculous bronchial stenosis who was subjected to bronchoplasty. The patient was a 33-year-old man who had stenosis of the left main bronchus. Because the lesion was associated with bronchomalacia, previous balloon dilatation therapy had failed. At thoracotomy, the left upper lobe was found not to be saved for the tuberculous lesion. Although there were many inflamed nodules in the left lower lobe due to repeated episodes of pneumonia, we decided to save it using bronchoplasty expecting its respiratory functional recovery. He ran uneventful course postoperatively and his lung function improved. We conclude that bronchoplasty may prove effective for patients with tuberculous bronchial stenosis associated with bronchomalacia; and thus, to avoid pneumonectomy, bronchoplasty should be attempted even if the reconstructed lung is mildly inflamed.
Adult↗
[Detection of telomerase activity and its clinical application].
Telomerase is a ribonuclear protein that is detected in more than 90% of primary cancer tissues using a telomeric repeat amplification protocol (TRAP) assay, thus, telomerase is considered to be a novel marker for cancer. Telomerase activity is not detectable in somatic cells, except for hematopoietic cells and cryptic cells in the intestine and hair follicles, thus, quantitation of telomerase is important to delineate clinical implication of telomerase activity. We have developed semiquantitative fluorescence-based TRAP assay. Moreover, we also developed an in situ TRAP assay that detects telomerase activity at the cellular level. Thus, using these TRAP assays, we are able to detect telomerase activity in various kinds of extracts or cytological specimens and therefore these applications may have additive information in the early detection of cancer and monitoring disease condition.
Adult↗
[Fluorine-18 labeled 6-fluoro-L-dopa: systematization and evaluation of its usefulness].
6-[18F]Fluoro-L-dopa (L-3,4-dihydroxy-6-[18F]fluorophenylalanine; 6-[18F]FDPA) is useful to assess presynaptic dopamine metabolism in central nervous system. In this paper, we report on the usefulness of the 6-[18F]FDOPA synthesis system developed for the routine synthesis. This system consists of the 6-[18F]FOPA synthesis and the separation units in conjunction with controller using a personal computer. The synthesis time of 6-[18F]FDOPA was 73 minutes. The typical yield and specific activity were 1.4-2.4 GBq and 244-270 MBq/mumol at the end of synthesis, respectively, under the irradiation condition of 50 microA for 130 minutes. The radiochemical yields of 6-[18F]FDOPA were 31.3-38.7% based on the [18F]acetylhypofluorite, and the results were affected with the condition of potassium acetate (AcOK) to produce gaseous [18F]acetylhypofluorite. This system is useful for the routine production of 6-[18F]FDOPA because of its high yield and high specific activity while maintaining AcOK in good condition, and decreasing the radiation exposure for chemist.
Brain↗
Clinical implications of telomerase activity levels in acute leukemia.
In the present study, we used the telomeric repeat amplification protocol assay, an internal telomerase assay standard, and an automatic DNA sequencer to detect and quantitate telomerase activity in blood samples obtained from normal and acute leukemia patients. Telomerase activity was analyzed in 78 acute leukemia patients and ranged from 0.65 to 147 relative to the internal standard. Compared to the age-matched normal levels of telomerase activity in the peripheral blood cells, we determined that 45 (81.8%) of 55 acute myeloid leukemia (AML) and 16 (69.6%) of 23 acute lymphoid leukemia patients had elevated telomerase activity. There was no relationship between peak telomere length and telomerase activity in both acute lymphoid leukemia and AML patients. In AML, the level of telomerase activity was associated with French-American-British subtypes and cytogenetics, and patients with elevated telomerase activity had high leukocyte counts and more frequent extramedullary involvement during the disease. Among 78 patients, 5 had high levels of telomerase activities similar to immortalized leukemia cell lines; these 5 patients had a very poor prognosis (P < 0.05). The levels of telomerase activity significantly decreased in patients in complete remission. Most of the patients in complete remission showed a normal level of telomerase activity; however, two of them had low to moderate telomerase activity, and they relapsed shortly after entering complete remission. In relapsed patients, there is a general trend for increased telomerase levels, and 2 of the 13 patients retained high telomerase activity, whereas the other 11 had normal to moderate telomerase activity. These results suggest that telomerase activity may be a useful additional method for monitoring the disease condition in acute leukemia patients.
Adolescent↗
Protein and RNA synthesis-dependent and -independent LTPs in developing rat visual cortex.
Multiple forms of synaptic potentiation have been described, but their involvement in development versus learning is unknown. To address this, we examined whether long-term potentiation (LTP) in visual cortex requires protein or RNA synthesis using slice preparations. Theta-burst stimulation of white matter induced two distinct types of LTP in layer 4. A slowly developing LTP, preferentially induced in juveniles, was blocked by protein and RNA synthesis inhibitors and was L-type calcium channel dependent. A quickly developing LTP, induced in juveniles and adults, was independent of macromolecular synthesis and required N-methyl-D-aspartate receptor activation. Thus, slow LTP might account for developmental plasticity in visual cortex including the activity-dependent refinement of neural circuitry while fast LTP might underlie the changes in synaptic strength that may participate in visual learning and memory.
2-Amino-5-phosphonovalerate↗
Optical responses evoked by white matter stimulation in rat visual cortical slices and their relation to neural activities.
To characterize optical responses (ORs) evoked by white matter (WM) stimulation in slices of rat visual cortex (VC) stained with voltage sensitive dyes, time course of ORs in each layer was investigated by recording ORs with a linearly aligned photodiode array, and the spatial patterns of the ORs at specified time after stimulation were investigated by a CCD camera in combination with stroboscopic illumination. The ORs recorded by the photodiode array were an increase in absorption at 700 nm and a decrease in the wavelength below 650 nm, suggesting that the ORs were dye related. The ORs were compared with field potentials (FPs) to clarify that neural events were represented by the ORs, and in support of this view, we found that the first order spatial differentials of ORs and that of FPs were in good agreement. We further compared ORs with intracellular responses, and found that the ORs mainly represent postsynaptic potentials (PSPs) of VC neurons except for the deeper part of layer VI, where a component representing action potentials in fibers stimulated directly was observed. The time-lapse imaging of ORs showed that excitation first propagated vertically up to layer I and subsequently in the horizontal direction along layers II-III and V-VI as in previous investigations. Spatio-temporal patterns of ORs under blockade of synaptic transmission were also investigated to reveal activity of fibers evoked by WM stimulation which produced such patterns of propagation.
Action Potentials↗
Trisomy 10 in acute myeloid leukemia.
We observed two patients with acute myeloid leukemia (AML) exhibiting trisomy 10 as the sole chromosome abnormality at the time of diagnosis. One patient was diagnosed with AML-MO, and the other with AML-M2. Both cases were CD7-antigen positive. However, we could not find any distinct clinico-hematologic characteristics of AML with trisomy 10 in these two patients. Trisomy 10 might be a rare recurring numerical chromosome abnormality and the incidence may be about 0.5% in de novo AML.
Aged↗
Inactivation of multiple tumor-suppressor genes involved in negative regulation of the cell cycle, MTS1/p16INK4A/CDKN2, MTS2/p15INK4B, p53, and Rb genes in primary lymphoid malignancies.
It is now evident that the cell cycle machinery has a variety of elements negatively regulating cell cycle progression. However, among these negative regulators in cell cycle control, only 4 have been shown to be consistently involved in the development of human cancers as tumor suppressors: Rb (Retinoblastoma susceptibility protein), p53, and two recently identified cyclin-dependent kinase inhibitors, p16INK4A/MTS1 and p15INK4B/MTS2. Because there are functional interrelations among these negative regulators in the cell cycle machinery, it is particularly interesting to investigate the multiplicity of inactivations of these tumor suppressors in human cancers, including leukemias/lymphomas. To address this point, we examined inactivations of these four genes in primary lymphoid malignancies by Southern blot and polymerase chain reaction-single-strand conformation polymorphism analyses. We also analyzed Rb protein expression by Western blot analysis. The p16INK4A and p15INK4B genes were homozygously deleted in 45 and 42 of 230 lymphoid tumor specimens, respectively. Inactivations of the Rb and p53 genes were 27 of 91 and 9 of 173 specimens, respectively. Forty-one (45.1%) of 91 samples examined for inactivations of all four tumor suppressors had one or more abnormalities of these four tumor-suppressor genes, indicating that dysregulation of cell cycle control is important for tumor development. Statistical analysis of interrelations among impairments of these four genes indicated that inactivations of the individual tumor-suppressor genes might occur almost independently. In some patients, disruptions of multiple tumor-suppressor genes occurred; 4 cases with p16INK4A, p15INK4B, and Rb inactivations; 2 cases with p16INK4A, p15INK4B, and p53 inactivations; and 1 case with Rb and p53 inactivations. It is suggested that disruptions of multiple tumor suppressors in a tumor cell confer an additional growth advantage on the tumor.
Adolescent↗
Tyrosine 425 within the activated erythropoietin receptor binds Syp, reduces the erythropoietin required for Syp tyrosine phosphorylation, and promotes mitogenesis.
Erythropoietin (Epo), the primary in vivo stimulator of erythroid proliferation and differentiation, acts, in part, by altering the tyrosine phosphorylation levels of various intracellular signaling molecules. These phosphorylation levels are tightly regulated by both tyrosine kinases and tyrosine phosphatases. We have recently shown that the SH2 containing tyrosine phosphatase, Syp, binds directly to both the tyrosine phosphorylated form of the Epo receptor (EpoR) and to Grb2 after Epo stimulation of M07e cells engineered to express high levels of human EpoRs (T. Tauchi, et al: J Biol Chem 270:5631, 1995). To determine which tyrosine within the EpoR is responsible for binding Syp, we examined DA-3 cell lines expressing full-length mutant EpoRs bearing tyrosine to phenylalanine substitutions for each of the eight tyrosines within the intracellular domain of the EpoR. We found that: (1) all Epo-stimulated mutant EpoRs, except for the Y425F EpoR, coimmunoprecipitated with Syp; (2) all Epo-stimulated mutant EpoRs, except for the Y425F EpoR, bound to a GST-fusion protein containing both SH2 domains of Syp; (3) Jak2 could phosphorylate GST-Syp in vitro after Epo stimulation of wild-type (wt) EpoR expressing DA-3 cells; (4) Epo-stimulated tyrosine phosphorylation of Syp in vivo was markedly reduced in Y425F EpoR expressing DA-3 calls; and (5) DA-3 cells expressing the Y425F EpoR grow less well in response to Epo than wt EpoR expressing cells. These results suggest that Syp binds via its SH2 domains to phosphorylated Y425 within the EpoR and is then phosphorylated on tyrosine residues by Jak2. Moreover, Y425 in the EpoR reduces the Epo requirement for Syp tyrosine phosphorylation and promotes proliferation.
Animals↗
Immobilized anti-KIT monoclonal antibody induces ligand-independent dimerization and activation of Steel factor receptor: biologic similarity with membrane-bound form of Steel factor rather than its soluble form.
Interaction of a tyrosine kinase type receptor and its ligand induces receptor-dimerization or -oligomerization followed by transphosphorylation and activation of its intrinsic kinase, which leads to a series of intracellular signals. We have previously reported that the membrane-bound form of Steel factor (SLF) induces more persistent tyrosine kinase activation and longer life span of c-kit encoded protein (KIT) than its soluble form (Miyazawa et al, Blood 85:641, 1995). In this study, we used YB5.B8 monoclonal antibody (MoAb) that recognizes the extracellular domain of KIT to investigate whether immobilized anti-KIT MoAb can substitute for SLF as a potent activator of KIT by cross-linking receptors and further compared its effect with each SLF isoform in a factor-dependent cell line M07e. YB5.B8 MoAb in a soluble state suppressed SLF-induced M07e cell proliferation in a dose-dependent manner. By contrast, once this antibody was immobilized on the goat-antimouse MoAb (GAM)-coated culture plates, it supported the growth of M07e cells in the absence of any growth factors, whereas culture the cells in GAM alone or YB5.B8 without GAM-coated plates resulted in rapid cell-death within 24 hours. As with the natural ligand SLF, immobilized YB5.B8 MoAb synergized with granulocyte-macrophage colony-stimulating factor (GM-CSF) in inducing cell proliferation compared with either YB5.B8 MoAb or GM-CSF alone. Immunoblotting with antiphosphotyrosine MoAb showed that interaction of M07e cells with immobilized YB5.B8 induced tyrosine phosphorylation of a series of intracellular proteins including KIT (145 kD). In addition, cross-linking studies using a water-soluble cross linking reagent bis-sulfosuccinimidyl-suberate showed that immobilized YB5.B8 MoAb induced dimerization and activation of KIT. However, as with stimulation by the membrane-bound form of SLF, the kinetics of KIT activation with YB5.B8 MoAb was more prolonged compared with the cells treated with recombinant soluble SLF. Flow cytometry showed that, unlike the cells treated with soluble SLF, no downmodulation of cell-surface KIT expression was observed in M07e cells cultured with immobilzed YB5.B8 MoAb. These data suggest that immobilized antibodies against hematopoietic receptors may replace their ligand-stimulators; however, their activities may resemble the membrane-bound form rather than the soluble form of natural ligands.
Amino Acid Sequence↗
Rapid fluorescence in situ hybridization on interphasic nuclei to discriminate between homozygous and heterozygous transgenic mice.
Homozygous and heterozygous transgenic mice of the Tg152 line overexpressing the human copper/zinc superoxide dismutase (hSOD-1) were rapidly differentiated by fluorescence in situ hybridization (FISH) using interphase lymphocyte nuclei. We have devised a simple and fast method for preparing interphase nuclei with very small quantities of whole mouse blood, avoiding several steps of the classical FISH technique. Lymphocyte separation and cell culture were not required. This technique provides an excellent tool for the unambiguous detection of homozygous and heterozygous transgenic mice in a litter. It can be used to check young animals since 2 microliters of whole blood is sufficient. We also show that in this transgenic line numerous copies of the hSOD-1 transgene are integrated at a single autosomal locus, in tandem head-to-tail organization.
Animals↗
Tl-201 uptake and retention in a Warthin's tumor.
We report scan findings of Tl-201 in a case of histologically proved Warthin's tumor. Dual isotopes acquisition was performed in a case of left parotid Warthin's tumor. Both early and delayed Tc-99m-pertechnetate (Tc-99m) images showed increased uptake at the tumor. Tl-201 scan also showed an increase of uptake on the early image and retention on the delayed image. The uptake ratios of Tl-201 were 3.0 (early) and 2.3 (delayed). Scan findings of Tl-201 in a case of Warthin's tumor were similar to those of Tc-99m, and the interpretation of Tl-201 images should be accompanied with Tc-99m images.
Adenolymphoma↗
Application of Tc-99m-tetrofosmin as a tumor imaging agent: comparison with Tl-201.
Tc-99m-tetrofosmin SPECT was performed on 6 occasions in 4 patients with hypopharyngeal carcinoma, lung carcinoma, esophageal carcinoma and maxillary plasmocytoma and compared with Tl-201 SPECT. All lesions accumulated both Tc-99m-tetrofosmin and Tl-201. Early uptake ratios of Tc-99m-tetrofosmin were about 2 but those of Tl-201 were much higher (more than 3). Washout rates of Tc-99m-tetrofosmin were higher than those of Tl-201. There was a good positive correlation between the early uptake ratio of Tc-99m-tetrofosmin and that of Tl-201. The delayed uptake ratio and washout rate showed poor correlation. In conclusion, early uptakes of both the agents were similar but their retention patterns were different. Tc-99m-tetrofosmin may be used for tumor imaging though more studies are required to evaluate diagnostic accuracy and the significance of delayed images.
Aged↗
Differentiation effect of acyclic retinoid on acute promyelocytic leukemia cells.
Acyclic retinoid (all-trans-3, 7, 11, 15-tetramethyl-2, 4, 6, 10, 14-hexadecapentaenoic acid) binds cellular retinoic acid-binding protein with an affinity similar to that of all-trans retinoic acid and induces differentiation of human hepatoma cell lines and a human acute myelogenous leukemia cell line (HL-60). We investigated the in vitro efficacy of acyclic retinoid to induce the differentiation of acute promyelocytic leukemia (APL) cells using primary cultured cells obtained from 11 APL patients. Five days' incubation with acyclic retinoid effected a dose-dependent induction of differentiation. Cells from eight patients showed maximum differentiation at 10(-6) M acyclic retinoid. Cells from one patient required 10(-5) M for maximum differentiation, while those from two patients exhibited moderate differentiation at 10(-5) M. Five days' incubation with acyclic retinoid (10(-7) approximately 10(-5) M) did not affect the viability or number of cells from any patient except one, whose cells showed a slight decrease in viability at 10(-5) M. Thus, we conclude that acyclic retinoid induced the differentiation of primary cultured APL cells at concentrations of 10(-6) approximately 10(-5) M, a range at which it is not toxic.
Antineoplastic Agents↗