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Biomedical subjects

N Takagi

Publications and source records attributed to N Takagi.

At least 163 records · Page 9Linked to original sources

[Anaphylactoid reaction after intravenous administration of Gd-DTPA].

An anaphylactoid reaction due to Gd-DTPA was observed in a patient who had disposition of asthma bronchiale. Five minutes after injection of Gd-DTPA, the patient developed laryngeal edema and erythema over the whole body. The patient recovered after treatment. It may be advisable to tighten indications for Gd-DTPA study on patients with allergic disposition. Gd-DTPA should be used with the same care against the anaphylactoid reaction as iodinated contrast media.

Adolescent↗

Effects of naftidrofuryl oxalate on microsphere embolism-induced changes in tricarboxylic acid cycle intermediates of rats.

The present study was undertaken to determine whether naftidrofuryl oxalate, a cerebral vasodilator, may improve or attenuate microsphere embolism-induced damage to the mitochondrial tricarboxylic acid cycle. For this purpose, the intermediates in the tricarboxylic acid cycle were determined using cerebral cortex isolated from microsphere-injected rats with and without naftidrofuryl oxalate treatment. Seven-hundred microspheres, with a diameter of 48 microns were injected into the right hemisphere through the right common carotid artery. The presence of cerebral infarction on the 3rd day after the operation was confirmed by the development of triphenyltetrazolium chloride-unstained areas in brain sections. Succinate, fumarate, malate, citrate and alpha-ketoglutarate, but not oxaloacetate, contents were significantly decreased in the right hemisphere of rats on the 3rd day following microsphere embolism. In the left hemisphere, a similar but smaller decrease in these intermediates was seen. The rats, which showed typical stroke-like symptoms, were treated with 15 mg/kg naftidrofuryl oxalate i.p., twice daily for 2.5 days, resulting in a significant reversal of the intermediate content of both hemispheres toward the control and an increased in the triphenyltetrazolium-stained area of a coronal section of the right hemisphere relative to the untreated animals. The results suggest that naftidrofuryl oxalate attenuates the development of microsphere embolism-induced cerebral infarction and improves microsphere-induced impairment of the mitochondrial tricarboxylic acid cycle. The observed effects provided evidence for a possible site of action of the agent on ischemic brain energy metabolism.

Animals↗

Aggressive rectal lymphoma of large granular lymphocytes with the histologic feature of an angiocentric growth pattern.

The authors report an unusual large cell lymphoma of the rectum composed of large granular lymphocytes (LGL) with histologic characteristics of an angiocentric growth pattern. Immunophenotyping showed that most of the tumor cells were CD3-, CD4-, CD8+, CD16+, CD56+, and CD57-. Fine structural analysis of the tumor cells found substantial numbers of electron-dense granules. Genotypic investigation showed a germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene. The clinical course was aggressive, with rapid dissemination to the lungs, liver, and subcutis. The lesion was resistant to chemotherapy. There was, however, no evidence for peripheral blood or bone marrow involvement. This case report demonstrates the need for continued inquiry into the possible association of LGL with angiocentric lymphoproliferative lesions and gut-associated T-lymphocyte lesions.

Adult↗

Cell fusion-induced quick change in replication time of the inactive mouse X chromosome: an implication for the maintenance mechanism of late replication.

It is unknown how and why the genetically inactivated mammalian X chromosome replicates late in S phase. There are also occasional inactive X chromosomes characterized by an opposite behavior replicating early in S phase. Two clonal cell lines, MTLB3 and MTLH8, isolated from a cultured murine T-cell lymphoma have an allocyclic X chromosome of the latter type. This precociously replicating X chromosome was judged to be genetically inactive as the late replicating one. Immediately after fusion with another cell line, the precociously replicating X chromosome from these cells starts to replicate late in S phase. This finding seems to suggest that late replication characterizing the inactive X chromosome is actively maintained by a trans-acting factor in female somatic cells, and that its lack entails a switch from late replication to precocious replication. It remains unknown whether this presumptive factor also modifies the autosomal replication pattern.

Animals↗

Application of 13C-labeling and nuclear magnetic resonance spectroscopy to pharmacokinetic research: measurement of metabolic rate of benzoic acid to hippuric acid in the rat.

The use of 13C-labeling and nuclear magnetic resonance (NMR) spectroscopy to trace the biotransformation of benzoic acid (BA) to hippuric acid (HA) in the rat has been described. Novel [2,4,6,7-13C4]BA, which was labeled in the specific protonated carbons, was used in order to enhance the sensitivity of 13C NMR detection on the basis of the nuclear Overhauser enhancement and short spin-lattice relaxation time. The urinary excretion of [2,4,6,7-13C4]HA formed from intravenously administered [2,4,6,7-13C4]BA was followed by proton-decoupled 13C NMR spectroscopy (only 10 min accumulation time) without any separation procedures such as extraction and chromatography, using [2-13C]sodium acetate as an internal standard for quantitation. The heights of resonances for C2,6 of [2,4,6,7-13C4]HA and C2 of the internal standard were used to calculate [2,4,6,7-13C4]HA concentration. The lower limit of measurable amounts (ca. 40 nmol) was found to be improved about one order of magnitude over that of the method using commercially available [7-13C]BA. In general, this tracer technique has the potential for wide application to pharmacokinetic research since xenobiotic and endogenous metabolism can be followed by very simple and convenient procedures.

Animals↗

Variable X chromosome inactivation patterns in near-tetraploid murine EC x somatic cell hybrid cells differentiated in vitro.

For the cytogenetic study of X chromosome inactivation as an X chromosome dosage compensation mechanism, we isolated a number of XXXX, XXX, and XXY near-tetraploid mouse hybrid cell clones by fusing XX or XO embryonal carcinoma cells with lymphocytes carrying a structurally altered X chromosome(s). The inactive X chromosome from the female lymphocyte was reactivated in these hybrid clones which retained embryonal carcinoma morphology so far as they were cultured on the collagen-coated plastic surface in the medium supplemented with leukemia inhibitory factor (LIF) and betamercaptoethanol (BME). Some of these clones developed balloon-like cystic embryoid bodies when they were allowed to form cell aggregates in medium without LIF and BME in bacteriological petri dishes to which they do not adhere. X chromosome inactivation occurring during this process detected by the incorporation of 5-bromodeoxyuridine did not conform to the expected pattern leaving two X chromosomes active in every tetraploid cells. This may suggest either that the X-inactivation mechanism evolved primarily, for the diploid cell is unable to deal with tetraploid conditions efficiently, or that the present system of in vitro differentiation represents an anomalous situation never encountered in vivo.

Animals↗

Flow injection analysis of formaldehyde leached from denture-base acrylic resins.

Formaldehyde is responsible for allergic inflammation in acrylic denture wearers and the quantitation of formaldehyde is necessary to study its leaching from denture-base materials. Flow injection analysis was developed to quantify the formaldehyde leached from acrylic resins. Different resins were immersed in aqueous solvents at 37 degrees C and the immersion solutions were directly injected into the flow system, in which formaldehyde was converted on-line to a fluorescent derivative and its fluorescence was detected. Under the optimized conditions, the leached formaldehyde could be quantified in a short time (within 4 min) with high sensitivity (pmol levels per injection) and high specificity (no fluorescent response to the other leachables). In leaching experiments, significant amounts of formaldehyde were leached from autopolymerized resins, but not from heat- and microwave-polymerized resins.

Acrylic Resins↗

Parental imprinting on the mouse X chromosome: effects on the early development of X0, XXY and XXX embryos.

To examine the effects of X-chromosome imprinting during early mouse embryogenesis, we attempted to produce XM0, XP0, XMXMY, XMXPY and XMXMXP (where XM and XP stand for the maternally and the paternally derived X chromosome, respectively) making use of mouse strains bearing the translocation Rb(X.2)2Ad and the inversion In(X)1H. Unlike XMXPY embryos, XMXMY and XMXMXP conceptuses suffered from severe growth retardation or abnormal development characterized by deficient extra-embryonic structures at 6.5-7.5 days post coitum (dpc). A cytogenetic study suggested that two XM chromosomes remaining active in certain nonepiblast cells were responsible for the serious developmental abnormality found in these embryos disomic for XM. Although matings involving females heterozygous for Rb(X.2)Ad hinted at the paucity of XP0 embryos relative to those having the complementary karyotype of XMXMXP, further study of embryos from matings between females heterozygous for In(X)1H and Rb2Ad males did not substantiate this observation. Thus, the extensive peri-implantation loss of XP0 embryos shown by Hunt (1991) may be confined to X0 mothers. Taken together, this study failed to reveal a parentally imprinted X-linked gene essential for early mouse embryogenesis other than the one most probably corresponding to the X-chromosome inactivation centre.

Animals↗

Identification and characterization of adenosine A1 receptor-cAMP system in human glomeruli.

Although adenosine is known to affect renal function through stimulating adenosine receptors, little is known about A1 receptors in human glomeruli. Thus, we attempted to identify the adenosine A1 receptor-cyclic AMP (cAMP) system in human glomeruli. Normal renal cortical tissues were obtained at nephrectomy of patients with renal cell carcinoma. Glomeruli were isolated using a graded sieving method or dissected manually under a stereomicroscope. Radioligand binding assay using 2-chloro-N-[3H] cyclopentyl adenosine ([3H]CCPA, an A1 agonist ligand) was performed at 30 degrees C for 90 minutes. Cyclic AMP (cAMP) produced in glomeruli was measured after incubation with different concentrations of N6-cyclohexyladenosine (CHA; A1 agonist) and a phosphodiesterase inhibitor. The specific binding was saturated within 60 minutes and reversible by adding 1 mM of theophylline. Scatchard plot analysis revealed a single class of binding site (Kd = 1.78 +/- 0.21 nM, Bmax = 271.7 +/- 35.8 fmol/mg protein). The specific binding was inhibited dose-dependently by various agents in an order suggesting A1 receptor specificity. CHA inhibited the production of cAMP in microdissected human glomeruli. This inhibitory effect was antagonized by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; A1 antagonist). This is the first study revealing the presence of the A1 receptor-cAMP system in human glomeruli using a radioligand binding assay method and by measuring the cAMP production.

Adenosine↗

Telomere change and loss of heterozygosity of mouse primary tumors and cell lines.

Changes in the number of telomere repeat arrays were examined in mouse tumor cells. Telomeres that function for the protection of chromosomes were detected as bands and a smear by pulsed field gel electrophoresis and gel-hybridization using (TTAGGG)4, as a probe. Of eight primary tumors induced in F1 mice between C57BL/6 and C3H/He and between C57BL/6 and MSM, three showed telomere alteration, two having extra bands and one having lost several telomere bands. The others exhibited patterns similar to those of normal tissues. However, the change was detected in all four cell lines that were established from one of the tumors. One cell line was further cloned and examined. Two of the nine clones differed in the telomere pattern. The telomere change was also observed in two other cell lines, FM3A cells and nontransformed BALB3T3 cells. These results suggest that telomeres are highly mutable in tumor cells and cultured cell lines. Three of the tumors and one cell line were analyzed for loss of heterozygosity with 51 microsatellite probes covering all 19 autosomes. Also, karyotype analysis of the cell line was performed. No allelic loss was seen and chromosomal abnormality was rare, although aneuploidy and imbalance in chromosomal number were observed. Possible involvement of the telomere changes observed here in chromosome impairment is discussed.

Animals↗

X chromosome retains the memory of its parental origin in murine embryonic stem cells.

A cytogenetic and biochemical study of balloon-like cystic embryoid bodies, formed by newly established embryonic stem (ES) cell lines having a cytogenetically or genetically marked X chromosome, revealed that the paternally derived X chromosome was inactivated in the majority of cells in the yolk sac-like mural region consisting of the visceral endoderm and mesoderm. The nonrandomness was less evident in the more solid polar region containing the ectodermal vesicle, mesoderm and visceral endoderm. Since the same was true in embryoid bodies derived from ES cells at the 30th subculture generation, it was concluded that the imprinting responsible for the preferential inactivation of the paternal X chromosome that was limited to non-epiblast cells of the female mouse embryos, was stably maintained in undifferentiated ES cells. Differentiating epiblast cells should be able to erase or avoid responding to the imprint.

Animals↗

Sustained changes in acetylcholine and amino acid contents of brain regions following microsphere embolism in rats.

The present study was undertaken to explore changes in neurotransmitters and neuromodulators of brain regions impaired by microsphere embolism-induced, sustained ischemia. Nine hundred microspheres (48 microns) were injected into the right internal carotid artery of rats, and the time course of changes in the triphenyltetrazolium chloride (TTC)-stained areas of their brain slices and acetylcholine and amino acid contents in the cerebral cortex, striatum and hippocampus of both hemispheres were determined. The TTC-unstained area, a measure of infarction, was developed in the right hemisphere by the 3rd day after the embolism, which was similar to that on the 28th day. A marked decline in acetylcholine content of these three regions of the right hemisphere was detected throughout the experiment (28 days). The glutamate, aspartate, GABA, and taurine levels were markedly decreased following microsphere-embolism. Most of these decreases were significantly attenuated during the first 5 days following the embolism, and they then partially recovered with time after the operation. Minor metabolic changes were observed in the left hemisphere. The results suggest that microsphere-embolism induces cerebral infarction and/or sustained damage to acetylcholine and neurotransmitter amino acid synthesis and/or catabolism of the brain regions. This model may provide information concerning the pathophysiological alterations in long-term cerebral ischemia and infarction.

Acetylcholine↗

Effect of an ultraviolet light-activated coating material on reduction of the leaching of methyl methacrylate and formaldehyde from denture acrylic resins.

Effect of glazing with an ultraviolet light-activated coating material on reduction of the leaching of methyl methacrylate and formaldehyde from denture acrylic resins was quantitatively evaluated. Disks prepared from auto-polymerized resins were painted with the material and radiated with ultraviolet light. The disks were immersed in artificial saliva and the concentrations of methyl methacrylate and formaldehyde leached were determined by high-performance liquid chromatography and flow injection analysis. Compared to untreated controls, the glaze significantly decreased concentrations of both leachable substances. Treatment with an ultraviolet light-activated coating material is effective in suppressing the leaching of methyl methacrylate and formaldehyde from acrylic resins as well as in smoothing the denture surfaces.

Acrylic Resins↗

[A case of type II cryoglobulinemia involving glomerulopathy associated with hepatitis C antibody].

We reported a case of type II cryoglobulinemia involving glomerulopathy associated with HCV-induced liver cirrhosis. The patient was a 57-year-old woman. Her past history included chronic hepatitis at 51 years and rheumatoid arthritis at 53 years of age. At 46 years, an erythematous lesion appeared on her legs, which was diagnosed as allergic vasculitis by skin biopsy. At 50 years, proteinuria, hematuria and hypertension were recognized. The next year, the first renal biopsy was performed and showed membranoproliferative glomerulonephritis (MPGN). Recently, the edema of her legs has progressed, and the laboratory data showed proteinuria, hematuria, hypocomplementemia, rheumatoid factor positivity, and increase of monoclonal IgG kappa chain. The second renal biopsy revealed an endocapillary proliferative glomerulonephritis-like lesion with marked infiltration of monocytes and macrophages. The subendothelial deposit showed a fine fibril-like pattern. She was treated with steroids and double filtration plasmapheresis (DFPP) therapy, but the treatment was not very effective. She died of liver cirrhosis, which was probably induced by hepatitis C virus (HCV), and sepsis. Generally, the patients of type II cryoglobulinemia often showed HCV antibody positivity, pointing to HCV as an etiological factor. In this case, renal biopsy was performed twice in the same patient, and the histologic findings suggest the clinicopathological course of cryoglobulinemia.

Chronic Disease↗

Inotropic effects of ryanodine and calcium antagonists on embryonic and hatched chick myocardium.

Effects of extracellular Ca2+ and inotropic agents on contractile force were examined in myocardial preparations from embryonic and hatched chicks. Measurement of contractile force was performed in an organ bath with whole hearts for the young embryo (5 to 6 days old) and with isolated strips from the right ventricles for the old embryos (16 to 18 days old), hatched chicks (within 24 hours after hatching) and 1 week old chicks. The extracellular Ca2+ concentration-contractile force curve was in a lower concentration range in young embryonic hearts when compared with older ones. 2 mM Ca2+ and 8 mM Ca2+ produced about 60% maximum contraction in preparations from young embryos and the older ages, respectively. The sensitivity to nicardipine and diltiazem was similar among all ages examined under 2 mM Ca2+. When the two drugs were applied to preparations from the older ages under 8 mM Ca2+, the sensitivity was lower than that of the young embryo under 2 mM Ca2+. Ryanodine produced a negative inotropic response at all ages but the effect was smaller in the young embryo when compared with those of older ages. Mn2+ produced a negative inotropic effect at all ages. In the older three ages, Mn2+ produced a late augmentation of the contractile force in addition to the initial negative inotropic response, while such augmentation was not observed in the young embryo. In conclusion, the chick myocardium was shown to undergo developmental changes in excitation-contraction mechanisms including increase in sarcoplasmic reticulum function during the embryonic period, and thus provides an interesting model for studies on excitation-contraction mechanisms.

Animals↗

A phenotypic and genotypic study of three node-based, low-grade peripheral T-cell lymphomas: angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma.

Phenotypic and genotypic findings were correlated and compared for 35 specimens taken from 34 patients with three specific types of low-grade peripheral T-cell lymphoma: lymphoepithelioid (LeL), angioimmunoblastic (AILD), and T-zone (TzL) lymphoma. Frozen sections were stained by the double immunoenzymatic method using a combination of the monoclonal antibody Ki-67 for proliferating nuclei and those against lymphocyte surface antigens. Data were correlated by observing clonal rearrangements in the genes of the T-cell receptor beta chain (TCR beta). Of the 35 specimens studied, 32 (91%) were of predominantly CD4+ helper cell proliferation, and 21 (60%) showed the TCR beta gene rearrangement. There were 15 cases of AILD and TzL with predominantly helper cell proliferation, which contained a minimum of 21% CD4+Ki-67+ cells based on the total number of cells present in the specimen. Of these, 13 (87%) showed TCR beta rearrangement. In eight cases, containing a maximum of 20% CD4+Ki-67+ cells, only one (13%) showed any rearrangement. In addition, TCR beta rearrangement was observed in five of the nine cases of LeL, including two cases with only 12% CD4+Ki-67+ cells. For each of the three types, the proportion of CD4+ cells among the Ki-67+ population showed a relatively good correlation with the clonal TCR beta gene rearrangement. Moreover, there was a significant difference (P less than 0.05) in survival curves between groups with and without TCR beta rearrangement, although no obvious plateau was seen. These results suggest that the paucity of tumor cells in these lesions may account for the absence of a detectable band of rearrangements in some patients with one of these three specific types of low-grade peripheral T-cell lymphoma.

Antigens, CD↗