[Morphological study of angiogenesis: transformation of fibroblasts into endothelial cells].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
K Kon
Publications and source records attributed to K Kon.
Gangliosides expressed in human breast cancer.
Breast tumors that were histopathologically diagnosed as invasive ductal carcinoma were examined in relation to their abnormal expression of gangliosides. Total ganglioside levels that were expressed as lipid-bound sialic acids were significantly higher in breast tumor tissues than in normal mammary tissues. Two kinds of unusual gangliosides were found to be expressed in many cases of breast tumors. One was a group of O-acetylated gangliosides, such as O-acetyl-GD3 and O-acetyl-GT3. They are known as fetal gangliosides, which appear in fetal brains. The other was an N-glycolylneuraminic acid-containing ganglioside, N-glycolyl-GM3, which had not been previously found in normal human tissues. The finding that unusual gangliosides are expressed in breast tumors may provide the basis for their immunological diagnosis and vaccine therapy.
Breast Neoplasms↗
A novel ganglioside, 9-O-acetyl GD1b, is recognized by serum antibodies in Guillain-Barré syndrome.
A hitherto undescribed ganglioside was detected in a crude ganglioside fraction of bovine brain using an IgM M-protein binding to Gal beta 1, 3GalNAc residue. We purified and identified it as 9-O-acetyl GD1b based on results of alkali treatment that yielded GD1b and results of fast atom bombardment-mass and gas chromatography-mass spectrometries. 9-O-acetyl GD1b was also found to be present in human peripheral nerve tissue. The reactivities of the serum antibodies from patients with Guillain-Barré syndrome to 9-O-acetyl GD1b, GD1b, and GM1 were determined by ELISA and TLC immunostaining. Nineteen of 85 serum samples from Guillain-Barré syndrome patients had antibodies that bound to 9-O-acetyl GD1b: 14 of the positive samples also reacted with GM1 and GD1b, three reacted with GM1 but not with GD1b, one with GD1b but not with GM1, and one with neither GM1 nor GD1b. These results show that a subset of patients with Guillain-Barré syndrome had antibodies that react with 9-O-acetyl GD1b; therefore, this ganglioside can serve as a target antigen against the antibodies present in Guillain-Barré syndrome.
Animals↗
[Neonatal brain injury and evoked potentials].
Marked abnormalities in ABR at discharge from NICU can predict overall prognosis in patients with neonatal asphyxia. However, in patients with neonatal asphyxia as a single risk factor, the incidence of ABR abnormalities was low and ABR was not indicative of their long-term prognosis. Over the past 10 years, we encountered 13 patients with deterioration of ABR and progressive hearing impairment after discharge from NICU. All patients showed severe cardiorespiratory symptoms in the neonatal period. Nine of thirteen patients were diagnosed as persistent neonatal pulmonary hypertension. Multimodal evoked potential studies could predict life expectancy and functional state in patients with severe motor and intellectual impairment. These kind of neurophysiological test can show the patients' functional state at the time of the examination. Discrepancies in evoked potentials and clinical symptoms provide important information regarding the pathophysiology of the patients.
Asphyxia Neonatorum↗
Chronic progressive mumps virus encephalitis in a child.
Explore the source record for details and available documents.
Adolescent↗
Characterization of four monosialo and a novel disialo Asn N-glycosides from the urine of a patient with aspartylglycosaminuria.
We previously reported for the first time two Japanese patients with aspartylglycosaminuria (AGU). A novel disialo Asn N-glycoside (AG-5) has been isolated from the urine of one of the patients in addition to four known monosialo Asn N-glycosides (AG-1 to AG-4) by gel filtration and anion exchange chromatography in this study. Final purification of AG-5 was achieved by an electrochemical chromatographic method, high performance liquid chromatography with pulsed amperometric detector (HPLC-PAD). The yield of AG-5 was approximately 1 mg l-1 urine. The chemical structures of AG-1 to AG-5 were characterized by gas-liquid chromatography, a permethylation study, fast atom bombardment-mass spectrometry (FAB-MS), and nuclear magnetic resonance (NMR). Based on the structural analysis, AG-5 had the following novel structure: NeuAc alpha 2-->8NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->Asn.
Acetylglucosamine↗
The structure of the core polyol of the ether lipids from Sulfolobus acidocaldarius.
The major ether-type lipid structures of Sulfolobus acidocaldarius (ATCC33909) were composed of caldarchaeol and calditoglycerocaldarchaeol. However, the characterization by nuclear magnetic resonance spectroscopy and mass spectrometry showed that the structure of calditol in calditoglycerocaldarchaeol is not nonitol, 2-(1',2',3'-trihydroxypropyl)1,2,3,4,5,6-hexahydroxyhexane, but 2-hydroxymethyl-1-(2,3-dihydroxypropoxy)2,3,4,5-cyclopentanetet raol with an ether linkage in the molecule. Such an intermolecular ether linkage was resistant to BCl3 treatment, but nonresistant to 57% HI degradation treatment conducted at 100 degrees C for 60 h, producing 2-hydroxymethyl-1,2,3,4,5-cyclopentanepentaol from calditol as reaction product. Further, it was confirmed that the structure of calditol is essentially a derivative of glycerol, and hydrocarbon chains were conjugated to the glycerol-like site in the structure. The calditol with an ether linkage in the molecule suggested an important role regarding the properties of heat-resistance and acid-resistance observed in Sulfolobales.
Acetylation↗
Structural analysis of a novel triphosphonoglycosphingolipid from the egg of the sea hare, Aplysia kurodai.
A novel phosphonoglycosphingolipid which contains three residues of 2-aminoethylphosphonate (2-AEP) was isolated from eggs of a sea gastropoid, Aplysia kurodai, and its structure was identified as follows. [see text] The major aliphatic components of ceramide were palmitic acid, stearic acid, 4-sphingenine, and 16-methyl-4-sphingenine. Antibodies which recognize 3-O-methylgalactose linked beta-glycosidically to phosphonoglycosphingolipids failed to react to the egg glycolipid. By comparing 1H-NMR spectra of native and HF-treated glycolipids, steric interactions of two residues of 2-AEP with ring protons of the glucose and the internal galactose were indicated.
Aging↗
[A rare case of true enterolith including a fruit seed].
Explore the source record for details and available documents.
Adult↗
N-acetylgalactosaminyl GD1a is a target molecule for serum antibody in Guillain-Barré syndrome.
Serum antibodies against such major glycolipids as GM1, GD1b, and LM1 have been reported in patients in the acute phase of Guillain-Barré syndrome (GBS). Because minor unidentified glycolipids also may be targets of antibodies in GBS sera, we assayed serum antibody against a crude ganglioside fraction using thin-layer chromatogram immunostaining. Antibody activity was detected against a band that migrated just below GD1a in 6 of the 50 patients with GBS tested. Antibody titer, as determined by enzyme-linked immunosorbent assay, decreased during the course of the disease. All 6 patients had suffered gastrointestinal infection before the neurological onset of GBS and showed low amplitudes for the compound muscle action potentials and normal or only slightly decreased nerve conduction velocities. Thin-layer chromatogram immunostaining did not show this antibody activity in any of the 16 normal and 119 disease controls. The unidentified glycolipid was isolated by DEAE-Sephadex A-25 column chromatography, sialidase treatment, and Iatrobeads column chromatography. Fast atom bombardment-mass spectra showed it to be N-acetyl-galactosaminyl GD1a.
Adult↗
Improved oral absorption of enteric coprecipitates of a poorly soluble drug.
An anticancer agent, N-[[[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]amino]carbonyl]-2 - nitrobenzamide (HO-221, 1), shows poor oral absorption and is only slightly soluble in water (0.055 microgram/mL at 37 degrees C). The coprecipitates with polyvinylpyrrolidone or a vinylpyrrolidone and vinylacetate copolymer (copolyvidone) showed a marked increase of the dissolution rate and attainment of temporary supersaturation of 1. The oral bioavailability of these preparations in dogs at a dose of 1 of 5 mg/kg was approximately 60%, which was 3.5 times greater than that of a micronized preparation. Further, the enteric coprecipitate with hydroxypropyl methylcellulose phthalate 200731, which showed a dissolution profile similar to that of the copolyvidone preparation at pH 6.5 but no dissolution at pH 1.2, revealed the almost complete oral absorption. Because intraduodenal administration of the copolyvidone coprecipitate showed a higher absorption than that of per oral administration, it was suggested that the partial precipitation of crystallites in the nonenteric coprecipitates occurred before reaching the absorption site, the small intestine.
Administration, Oral↗
Facile methods for isolation and determination of gangliosides in a small scale: age-related changes of gangliosides in mouse brain synaptic plasma membranes.
A quantitative isolation method for gangliosides from small sizes of samples has been developed. Total lipids were separated into gangliosides and other lipids using Phenyl Sepharose column chromatography. Gangliosides were recovered in a yield of 99%. Determination of gangliosides was performed by gas chromatography--mass spectrometry using a selected ion-monitoring technique. These combined methods can provide quantitative isolation and determination of gangliosides from as little as 10 mg fresh brain tissues or 0.5 mg protein of membrane fractions. The present methods were successfully applied to the analysis of gangliosides from mouse brain synaptic plasma membranes to reveal that the ganglioside contents and composition remain constant from adult to senescence.
Aging↗
Transformation of fibroblasts into endothelial cells during angiogenesis.
Light- and electron-microscopic autoradiography have been used to study fibroblast transformation into endothelial cells in the formation of new blood vessels during wound healing in rabbit ear chambers. When cultured fibroblasts labeled with tritium thymidine were transplanted autologously into the chambers, newly formed blood vessels contained endothelial cells labeled with tritium thymidine. This result suggests that fibroblasts play a pivotal role in angiogenesis, as progenitors of endothelial cells in newly formed blood vessels.
Animals↗
Antitumor effects of IST-622, a novel synthetic derivative of chartreusin, against murine and human tumor lines following oral administration.
The antitumor effects of 6-O-(3-ethoxypropionyl)-3',4'-O-exo- benzylidenechartreusin (IST-622), a new synthetic derivative of chartreusin (CT), were investigated. Following oral administration, IST-622 showed marked antitumor effects against various mouse tumors such as P388 and L1210 leukemias, B16 melanoma, Lewis lung carcinoma, Colon 26 and Colon 38 adenocarcinomas, and M5076 reticulum-cell sarcoma. The best antitumor effects were obtained by five intermittent treatments given every 4 days. In addition, IST-622 showed a significant growth-inhibitory effect against two human tumor xenografts, a large-cell lung cancer (Lu-116) and a gastric adenocarcinoma (St-4), among the seven lines tested. IST-622, which was rapidly metabolized into 3',4'-O-exo-benzylidenechartreusin (A-132) and not into CT in vivo or in culture medium, exhibited remarkable growth-inhibitory activity against P388 leukemia in vitro, its 50% growth-inhibitory concentration (IC50) being over 20-fold lower than that of CT. IST-622 showed an in vivo antitumor effect superior to that of authentic A-132, possibly resulting from a higher absorption ratio of IST-622 through the gastrointestinal tract. IST-622 is now under clinical phase I study in Japan.
Administration, Oral↗
Inhibition of K+ channels by chlorpromazine in rat ventricular myocytes.
Isolated rat ventricular myocytes were investigated with the whole-cell patch-clamp technique. Chlorpromazine inhibited inward-rectifying K+ currents (IC50 = 6.1 microM), time-independent outward currents (IC50 = 16 microM) and transient outward K+ currents. In the latter case, 100 microM of chlorpromazine reduced the amplitude of the peak current recorded at a clamp potential of 50 mV from 2.14 +/- 0.59 nA to 1.38 +/- 0.20 nA (n = 4) and decreased the time course of fast inactivation from 8.29 +/- 1.17 msec to 4.01 +/- 0.90 msec (n = 4). In addition, chlorpromazine blocked the ATP-dependent K+ current, which was activated either by the channel opener rilmakalim (10 microM) or by metabolic inhibition with carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP, 500 nM; IC50 for rilmakalim = 2.5 microM; IC50 for FCCP = 11.5 microM). The drug caused marked depolarization of the resting potential at higher concentrations (50 microM) from -79 +/- 3 mV to -27 +/- 11 mV (n = 4). The reversibility from channel block was slow and only partial for time-independent currents, especially inward-rectifying K+ currents, but it was relatively fast and complete for time-independent currents. Thus chlorpromazine blocks a variety of K+ channels in heart muscle cells. Inasmuch as the potency of inhibition is less than the previously reported use-dependent block of Na+ channels, the cardiovascular adverse effects of chlorpromazine are probably caused mainly by the latter effect.
Animals↗
[Juvenile Parkinson's disease initially presenting as bulbar incoordination: a case report].
We report a case of juvenile Parkinson's disease which initially presented as bulbar incoordination at the age 12. The condition was characterized by dystonia of the upper extremities. The patient was a 14-year-old female. The patient's main symptoms were bulbar dysfunction. Resting and action tremor, akinesia, stooped posture, distortion of the trunk, dystonia of the upper extremities, oculogyric crisis, and impairment of the postural reflex were seen. The bulbar symptoms were considered to be attributable to circumoral uncoordination. Although L-dopa decarboxylase inhibitors were markedly effective in alleviating these symptoms, an adverse reaction due to the agent was observed as the form of oral dyskinesia. Since the changes in blood concentration of L-dopa after administration of the agent was clearly reflected in the surface electromyogram, we concluded that this diagnostic procedure is useful in evaluating the therapeutic efficacy of L-dopa.
Adolescent↗
A novel ganglioside with a free amino group in bovine brain.
A novel ganglioside which binds cholera-toxin B-subunit was purified from bovine brain by an h.p.l.c. system using an Aquasil column subsequent to Q-Sepharose column chromatography. T.l.c./immunostaining showed that the isolated ganglioside had about 60% of the binding reactivity of the authentic ganglioside GM1 for cholera-toxin B-subunit. On h.p.l.c., this ganglioside migrated between ganglioside GD1a and GD1b, and was found to give positive reactions with ninhydrin and fluorescamine reagents which specifically react with amino groups. The presence of a free amino group was further confirmed by chemical re-N-acetylation. The N-acetylated product had an identical RF value on h.p.l.c. and similar reactivity with cholera-toxin B-subunit as the authentic GM1. H.p.t.l.c., t.l.c./immunostaining, negative-ion fast-atom-bombardment (f.a.b.)-m.s., and 1H-n.m.r. spectroscopy of the novel ganglioside unequivocally demonstrated that it has the basal structure of GM1 with de-N-acetylated neuraminic acid instead of N-acetylneuraminic acid. In the present study we report for the first time that a ganglioside derivative containing de-N-acetylated neuraminic acid, de-N-acetylated GM1, exists in natural brain tissues.
Acetylation↗
Novel lacto-ganglio type gangliosides with GM2-epitope in bovine brain which react with IgM from a patient of the amyotrophic lateral sclerosis-like disorder.
A motor neuron disorder resembling that of amyotrophic lateral sclerosis was found in a patient who had received the intramuscular administration of a mixture of bovine brain gangliosides (Yuki, N., Sato, S., Miyatake, T., Sugiyama, K., Katagiri, T., and Sasaki, H. (1991) Lancet 337, 1109-1110). A very high titer of anti-GM2 IgM was detected in the patient's serum and the patient quickly recovered after plasmapheresis. The clinical course of the patient appeared to be different from amyotrophic lateral sclerosis and the anti-GM2 IgM was thought to be the culprit. The IgM reacted with GM2, GM1b-GalNAc, SPG(alpha 2-3)-GalNAc, and GD1a-GalNAc, but not with GA2 or GD2, meaning that the epitope recognized by the IgM was the GM2-like terminal structure, GalNAc beta 1-4(Neu-Ac alpha 2-3)Gal beta 1-. In this study, we found two novel GM2-epitope containing gangliosides, X1 and X2, in bovine brain gangliosides by TLC immunostaining using the patient's IgM. They were characterized as unique lacto-ganglio type gangliosides containing the following branching structures. [formula: see text] Their unusual structures may be immunogenic to humans to induce anti-GM2 antibody.
Aged↗