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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 217 records · Page 12Linked to original sources

[Clinical features of essential thrombocythemia in three children].

Essential thrombocythemia (ET) is one of the quite rare myeloproliferative disorders in children. The natural course and outcome of this disease have been reported to vary. We report three children (two boys and one girl, mean age at diagnosis 12 yr) with ET who showed different clinical courses. The girl was asymptomatic, but the boys had ankle pain and priapism, respectively. The platelet count ranged between 2300 and 2900 x 10(9)/L, and the diagnoses were made according to the criteria of the Polycythemia Vera Study Group. The serum thrombopoietin level reached 0.33 and 0.47 fmol/ml in two patients. All three children were administered aspirin or dipyridamole orally. Normalization of the platelet count was observed in two patients, and stable disease persisted in one. The 12 pediatric patients with ET reported previously in Japan demonstrated a low incidence of serious thrombohemorrhagic complications and a favorable outcome, none developing acute leukemia. Careful continuous observation and conservative treatment may be preferable in pediatric patients who do not have cardiovascular symptoms, avoiding the use of potential leukemogens such as alkylating agents and hydroxyurea.

Aspirin↗

Successful treatment of disseminated Fusarium infection in an infant with leukemia.

Disseminated Fusarium infection in an immunocompromised host is intractable and results in high mortality. We provide the first full case report on successful treatment of a disseminated Fusarium infection in an infant. The 6-month-old infant, whose family raised livestock, had infantile leukemia. During the neutropenic period after intensive chemotherapy, vomiting, diarrhea, fever, subcutaneous nodes, and coughing appeared. Pneumonia was diagnosed, and Fusarium moniliforme was isolated from blood culture. A central venous catheter was removed. Granulocyte colony-stimulating factor (G-CSF) and amphotericin B (AMPH-B) (total dose, 65 mg/kg) were administered continuously for 8 weeks. The infection was resolved according to improvement of clinical and laboratory findings, and intensive chemotherapy was restarted for the leukemia. Cord blood stem cell transplantation from an unrelated donor was performed. The Fusarium infection did not recur, but after transplantation, leukemia relapsed. Treatment of neutrophils using G-CSF, AMPH-B, and local treatment induced resolution of the disseminated Fusarium infection in this immunocompromised host with malignancy. We suggest caution for patients living in an environment conducive to the development of Fusarium infection because of the particular risk of infection.

Amphotericin B↗

[Changes of autonomic functions by endoscopic upper thoracic sympathectomy on idiopathic hyperhidrosis].

Changes of autonomic functions before and after bilateral endoscopic upper thoracic sympathectomy (EUTS) were evaluated in 13 patients with idiopathic hyperhidrosis, with the sympathetic skin response, coefficient of variation of R-R intervals, mean heart rate, thermography, and non-invasive Valsalva test of the tonometry method. EUTS electronically destructs the upper thoracic sympathetic ganglions which innervate the upper extremities, and partially the heart. The decrement of mean heart rate, and persistent inhibition of the vascular contraction and hidrosis of the hands appeared after EUTS. These manifestations were effect produced by the abortion of sympathetic activity by EUTS. In 10 of the 12 cases, the baroreceptor sensitivity index II of Valsalva test which reflects the sympathetic autonomic nervous function of the heart showed normal pattern after EUTS. Four cases revealed reincrement of both the blood pressure and heart rate at the latter half phase of the second stage of the Valsalva test. The sympathetic dysfunction of the heart was limited to the decrement of mean heart rate although EUTS partially destroys sympathetic fibers innervating the heart. A long-term study is necessary to evaluate the effect of EUTS on the cardiac function.

Adolescent↗

Auranofin inhibits interleukin-1beta-induced transcript of cyclooxygenase-2 on cultured human synoviocytes.

The aim of this study was to characterize the effects of auranofin (2,3,4,6-tetra-O-acetyl-l-thio-beta-D-gluco-pyranosato-S) on cyclooxygenase expression and prostaglandin E(2) synthesis on cultured human synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with auranofin in the presence or absence of interleukin-1beta. Cultured supernatants were harvested for prostaglandin E(2) synthesis. Cyclooxygenase-1 and -2 expression was analyzed with Western and Northern blotting. Translocation of nuclear factor-kappa B p65 was determined by immunostaining. Cytotoxicity was measured with 51Cr release assay. Auranofin attenuated interleukin-1beta-induced prostaglandin E(2) production of the cells in a dose-dependent fashion. Auranofin selectively suppressed interleukin-1beta-induced cyclooxygenase-2 mRNA and protein expression of the cells without alteration of cyclooxygenase-1 expression. Also, auranofin interfered with interleukin-1beta-induced translocation of nuclear factor-kappa B. These inhibitory effects did not originate in the cytotoxicity of the agent. Our data indicate that auranofin inhibits interleukin-1beta-induced prostaglandin E(2) synthesis and cyclooxygenase-2 expression via suppression of nuclear factor-kappa B activation on synoviocytes.

Auranofin↗

Macrolide antibiotics protect against immune complex-induced lung injury in rats: role of nitric oxide from alveolar macrophages.

Macrolide antibiotics have unique immunomodulatory actions apart from antimicrobial properties. We studied the effects of macrolides on IgG immune complex (IgG-ICx)-induced lung injury in rats in vivo and in vitro. Intrapulmonary deposition of IgG-ICx produced a time-dependent increase in the concentration of NO in exhaled air. There were corresponding increases in the number of neutrophils accumulated into alveolar spaces, and lung wet-to-dry weight ratio. All of these changes were inhibited by pretreatment with erythromycin or josamycin, but not by amoxicillin or cephaclor. Incubation of cultured pulmonary alveolar macrophages caused up-regulation of NO production and expression of inducible NO synthase mRNA, an effect that was dose dependently inhibited by erythromycin, roxithromycin, or josamycin. The macrolides also reduced IgG-ICx-induced release of IL-1beta and TNF-alpha, but did not alter the release of NO induced by exogenously added IL-1beta and TNF-alpha. These results suggest that macrolide antibiotics specifically inhibit immune complex-induced lung injury presumably by inhibiting cytokine release and the resultant down-regulation of inducible NO synthase gene expression and NO production by rat pulmonary alveolar macrophages.

Animals↗

Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using (125)I-labeled anti-endoglin monoclonal antibodies.

Endoglin (CD105), which is a component of the TGF-beta receptor complex, is highly expressed at the surface of proliferating human endothelial cells such as those of tumor vessels. In the present study, we tested the antitumor efficacy of (125)I-labeled anti-endoglin monoclonal antibodies (MAbs), SN6f and SN6j, against s. c. tumors of MCF-7 human breast cancer cells in SCID mice by i.v. administration. SN6f and SN6j cross-react weakly with mouse endothelial cells, but show no significant reactivity with MCF-7 tumor cells. These MAbs are effectively internalized into the cells after binding to the cell surface antigen of endothelial cells. Four groups of SCID mice (n = 10 or 9 in each group) inoculated s.c. with 8 x 10(6) MCF-7 cells were treated with (125)I-SN6f (10 microCi), (125)I-SN6j (10 microCi), a (125)I-labeled isotype-matched control IgG (10 microCi) or PBS. The systemic therapy was performed in 2 series, i.e., on days 3, 5, 7 and days 58, 60, 62. Both (125)I-SN6f and (125)I-SN6j showed significant growth suppression of the tumors, whereas the (125)I-labeled control IgG did not show any significant antitumor efficacy. No significant toxicity or weight loss was observed in mice treated with either (125)I-SN6f or (125)I-SN6j. After 100 days of observation, autopsies revealed no significant organ damage. Our results show the possible usefulness of antiangiogenic radioimmunotherapy using (125)I-labeled anti-endoglin MAbs.

Animals↗

Aberrant plasticity in Alzheimer's disease.

Alzheimer's disease (AD) is a region-specific degenerative disease that mainly impairs the temporal and parietal lobes, with preservation of the frontal lobes until advanced stages of disease. Since [11C]diacylglycerol PET facilitates examination of loci exhibiting plasticity, it was performed in eight patients with AD and six age-matched normal control subjects to evaluate frontal lobe function. [11C]Diacylglycerol tomograms obtained from patients with AD demonstrated strong spotty incorporation of [11C]diacylglycerol mainly in the frontal association areas. However, [18F]fluorodeoxyglucose tomograms exhibited region-specific findings such as decreased CMRGIc in the parietotemporal association areas, which are involved in impairment of cognitive function. The strong spotty incorporation of [11C]diacylglycerol suggested a compensatory plastic process in the frontal lobes in response to involvement by Alzheimer's disease of the posterior association areas.

Adult↗

A novel acyl-CoA oxidase that can oxidize short-chain acyl-CoA in plant peroxisomes.

Short-chain acyl-CoA oxidases are beta-oxidation enzymes that are active on short-chain acyl-CoAs and that appear to be present in higher plant peroxisomes and absent in mammalian peroxisomes. Therefore, plant peroxisomes are capable of performing complete beta-oxidation of acyl-CoA chains, whereas mammalian peroxisomes can perform beta-oxidation of only those acyl-CoA chains that are larger than octanoyl-CoA (C8). In this report, we have shown that a novel acyl-CoA oxidase can oxidize short-chain acyl-CoA in plant peroxisomes. A peroxisomal short-chain acyl-CoA oxidase from Arabidopsis was purified following the expression of the Arabidopsis cDNA in a baculovirus expression system. The purified enzyme was active on butyryl-CoA (C4), hexanoyl-CoA (C6), and octanoyl-CoA (C8). Cell fractionation and immunocytochemical analysis revealed that the short-chain acyl-CoA oxidase is localized in peroxisomes. The expression pattern of the short-chain acyl-CoA oxidase was similar to that of peroxisomal 3-ketoacyl-CoA thiolase, a marker enzyme of fatty acid beta-oxidation, during post-germinative growth. Although the molecular structure and amino acid sequence of the enzyme are similar to those of mammalian mitochondrial acyl-CoA dehydrogenase, the purified enzyme has no activity as acyl-CoA dehydrogenase. These results indicate that the short-chain acyl-CoA oxidases function in fatty acid beta-oxidation in plant peroxisomes, and that by the cooperative action of long- and short-chain acyl-CoA oxidases, plant peroxisomes are capable of performing the complete beta-oxidation of acyl-CoA.

Acyl-CoA Dehydrogenase↗

Ovalbumin in developing chicken eggs migrates from egg white to embryonic organs while changing its conformation and thermal stability.

Ovalbumin was detected in developing chicken eggs. The large majority of these ovalbumin molecules was found to be in a heat-stable form reminiscent of S-ovalbumin. About 83 and 90% of the ovalbumin population was in a heat-stable form in day 14 or stage 40 amniotic fluid and day 18 or stage 44 egg yolk, respectively, whereas ovalbumin in newly deposited eggs was in the heat-unstable, native form. Purified preparations of stable ovalbumin from egg white and amniotic fluid showed a less ordered configuration than native ovalbumin, as analyzed by circular dichroism and differential scanning calorimetry. In addition, mass spectrometric analysis exhibited distinct size microheterogeneity between the stable and native forms of ovalbumin. Immunohisotochemical study revealed that ovalbumin was present in the central nervous system and other embryonic organs. These results indicated that egg white ovalbumin migrates into the developing embryo while changing its higher order structure.

Amino Acid Sequence↗

Wall cytoarchitecture of the rat ciliary process microvasculature revealed with scanning electron microscopy.

Ciliary process vasculature has an important role in aqueous humor production. There have been, however, few reports describing the overall cytoarchitecture of ciliary process vasculature. The wall cytoarchitecture of microvessels in the rat ciliary process was elucidated by scanning electron microscopy after removal of ciliary epithelia and connective tissue components with HCl hydrolysis. Utilizing characteristics of cellular morphology and vessel diameters, several vascular components were identified along the vascular tree: 1) arterial iridociliary circles (30-60 microm in outer diameter), containing a compact layer of circularly oriented spindle-shaped smooth muscle cells; 2) the proximal part of the radial ciliary arteriole (10-25 microm), containing a less compact layer of circularly oriented branched-smooth muscle cells and spindle-shaped smooth muscle cells; 3) a middle part of the radial ciliary arteriole (20-35 pm), with circularly oriented branched-smooth muscle cells and irregularly oriented stellate cells with ramifying projections; 4) a distal part of the radial ciliary arteriole (10-20 microm), possessing irregularly oriented stellate cells with ramifying projections; 5) marginal venules (15-20 microm), with spidery pericytes possessing highly ramifying and overlapped projections; 6) capillaries in the ciliary process (4-7 microm), with widely scattered pericytes having longitudinal and several circular projections; 7) venules in the posterior basal region of the ciliary process (greater than 5 microm), with widely scattered pericytes having a few thin projections. From arterial iridociliary circles to venules in the basal region of ciliary process, seven parts could be recognized by wall cytoarchitecture, which was discussed in relation with the function.

Animals↗

Multiple functional proteins are produced by cleaving Asn-Gln bonds of a single precursor by vacuolar processing enzyme.

Precursor-accumulating vesicles mediate transport of the precursors of seed proteins to protein storage vacuoles in maturing pumpkin seeds. We isolated the precursor-accumulating vesicles and characterized a 100-kDa component (PV100) of the vesicles. Isolated cDNA for PV100 encoded a 97,310-Da protein that was composed of a hydrophobic signal peptide and the following three domains: an 11-kDa Cys-rich domain with four CXXXC motifs, a 34-kDa Arg/Glu-rich domain composed of six homologous repeats, and a 50-kDa vicilin-like domain. Both immunocytochemistry and immunoblots with anti-PV100 antibodies showed that <10-kDa proteins and the 50-kDa vicilin-like protein were accumulated in the vacuoles. To identify the mature proteins derived from PV100, soluble proteins of the vacuoles were separated, and their molecular structures were determined. Mass spectrometry and peptide sequencing showed that two Cys-rich peptides, three Arg/Glu-rich peptides, and the vicilin-like protein were produced by cleaving Asn-Gln bonds of PV100 and that all of these proteins had a pyroglutamate at their NH2 termini. To clarify the cleavage mechanism, in vitro processing of PV100 was performed with purified vacuolar processing enzyme (VPE). Taken together, these results suggested that VPE was responsible for cleaving Asn-Gln bonds of a single precursor, PV100, to produce multiple seed proteins. It is likely that the Asn-Gln stretches not only provide cleavage sites for VPE but also produce aminopeptidase-resistant proteins. We also found that the Cys-rich peptide functions as a trypsin inhibitor. Our findings suggested that PV100 is converted into different functional proteins, such as a proteinase inhibitor and a storage protein, in the vacuoles of seed cells.

Amino Acid Sequence↗

Neural features of recovery from CNS injury revealed by PET in human brain.

Dysfunction of the brain occurring after local brain injury often improves clinically; however, the reason for this improvement has not been scientifically clarified. We used a new technique for imaging phosphoinositide turnover, carbon-11-labeled diacylglycerol-positron emission tomography, to observe the process of recovery from injury in human brain. Patients with local brain injury exhibited radioactive spots located in the association areas distant from the lesion, while normal controls did not exhibit such spots. These findings indicated one of possible features of the neural recovery from the central nervous system injury, which appears to play a role in modulation of synaptic transmission in the intact brain. Conventionally, attention has been directed primarily to areas surrounding brain injury, such as the penumbra; however, the present study suggests that initiation of reorganization of neural connections occurs in remote cortex.

Adult↗