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Biomedical subjects

Y Itagaki

Publications and source records attributed to Y Itagaki.

At least 37 records · Page 2Linked to original sources
PubMed1997

Detection of new spider toxins from a Nephilengys borbonica venom gland using on-line mu-column HPLC continuous flow (FRIT) FAB LC/MS and MS/MS.

Spider venom glands store various novel neurotoxic acylpolyamines which present potent and irreversible inhibition of the glutamatergic synapses. We have developed a new highly sensitive analytical method to detect and characterize structures of those neurotoxins stored in a single venom gland using micro bore column high performance liquid chromatography (HPLC)-continuous flow FRIT fast atom bombardment mass spectrometry (HPLC-FAB/MS) and tandem mass spectrometry (MS/MS) array detection system. The high-energy collision induced dissociation (CID) spectra of sodium cationized spider toxins produced very strong structurally informative product ions which afforded the location of nitrogen atoms and the connectivity of methylene units within the polyamines. This methodology permitted detection of 40 amino acid containing acylpolyamines in the venom of Nephilengys borbonica from which structures of only five compounds were previously known.

Animals↗
PubMed1997

Mass spectrometric structure determination of spider toxins: arginine-containing acylpolyamines from venoms of Brazilian garden spider Nephilengys cruentata.

A new strategy to characterize glutaminergic blocker acylpolymines stored in a spider venom with mass spectrometry is described. The crude spider venom extracts are amenable to direct MALDI mass spectrometry analysis which provides a rapid and accurate means of measuring the molecular weights of acylpolyamines without the isolation of individual samples. Compared with the previously developed mu-column HPLC/MS method, this procedure provides more efficient detection and identification of complex venom constituents. Twenty-five acylpolyamines were detected from Brazilian garden spider Nephilengys cruentata crude venom extracts by both HPLC/MS and MALDI-mass spectrometry. These acylpolyamine structures were determined by high-energy collision induced dissociation MS/MS method. Most of the compounds were classified into the previously reported generalized structures types A to D, which were found from the venom of Nephilengys borbonica. The structures of four acylpolyamines (M + H)+, m/z 623, 646, 688, and 745, which were not contained in the venom of Nephilengys borbonicare were determined to have arginine at the polyamine chain terminal and were named NPTX-622, -645, -687, and -744, respectively.

Animals↗
PubMed1997

Pure red cell aplasia during carbamazepine monotherapy.

A 7-year-old girl developed pure red cell aplasia during carbamazepine (CBZ) monotherapy for epilepsy. She developed generalized clonic convulsions at the age of 7 years and 8 months. Treatment with CBZ was begun. Two months later she was admitted to our hospital because of severe anemia. Bone marrow examination revealed the almost complete absence of erythroblasts, with normal myelopoiesis and megakaryocytopoiesis, indicating pure red cell aplasia. Following the discontinuation of CBZ, she developed brisk reticulocytosis within 1 week and her hemoglobin level rose to a normal one within 1 month. Although the hematological toxicity of CBZ is well documented, isolated cessation of red cell production is uncommon. A patient who is undergoing treatment with CBZ should be carefully monitored, especially for serious adverse reactions including pure red cell aplasia.

Anticonvulsants↗
PubMed1997

[Characterization of spider venom by mass spectrometry, construction of analytical system].

Spiders belonging to the genera, Nephila, Nephilengys, Araneus, etc., possess various polyamine toxins in their venom glands which paralyze insects by blocking the nerve-muscle signal transduction of glutaminergic synapses. More than 50 kinds of polyamine toxin analogs have been characterized which consist, in general, of the aromatic or heteroaromatic moiety connected with the combination of various types of polyamine chains. We are developing a new analytical system by means of a modern mass spectrometric technique which satisfies more rapid, highly sensitive and simple clean-up procedure without complicated chromatographic treatment. The trial of such approach has been performed by employing crude spider venom as the model material. This review article concerns with such proceeding of mass spectrometric analysis by microcolumn HPLC hyphenated FAB-MS system, continuous flow FAB-MS/MS system with high energy collision charge-remote fragmentation, solid and liquid matrix assisted laser desorption ionization (MALDI- and liquid MALDI-) technique connected with tandem mass spectrometer performing in the institute and in addition, femto-molar characterization of new spider venom spider polyamine toxins as a result of the application of such new techniques is addressed.

Animals↗
PubMed1997

[Effects of photodegradation of nifedipine on dog erythrocyte membranes].

We studied the effects of nifedipine (NF) on UV-induced photohemolysis of erythrocytes in vitro. A suspension in physiologic saline of crythrocytes separated from the venous blood sample freshly obtained from a dog was prepared and used. NF is a photolabile agent, and this drug was extremely sensitive to the long wavelength (365 nm) of UV light. The most abundant photodegradation product was a nitroso-derivative which changed into a lactam-derivative in the dog erythrocyte suspension with or without irradiation. NF itself showed protective effects against photohemolysis of erythrocytes caused by 365 nm of UV light as well as hypotonic hemolysis. But NF enhanced the degree of photohemolysis under oxygen condition. The photohemolysis enhanced by NF was reduced by thiobarbituric acid, indicating an oxidative stress by a radical intermediate of NF to photohemolysis. On the other hand, the nitroso-derivative reacted with erythrocyte hemoglobin spectroscopically to change into the lactam-derivative. It is considered that NF is a phototoxic agent to cause photohemolysis by producing a radical intermediate with oxygen and unknown species of hemoglobin degraded with the nitroso-derivative of nifedipine photoproduct.

Animals↗
PubMed1996

Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin, mitomycin C, and ultraviolet light.

The Y box-binding protein (YB-1) binds to DNA sequences, present in the control regions of many genes, that contain an inverted CCAAT box. The binding activity of a nuclear factor, designated MDR-NF1, to an inverted CCAAT box in the promoter of the multidrug resistance 1 (MDR1) gene has previously been shown to be increased in nuclear extracts of cells exposed to UV radiation or various anticancer agents. The MDR-NF1 cDNA has now been cloned by screening a human colon library with an active fragment of the MDR1 promoter. The amino acid sequence encoded by the cloned cDNA was identical to that of YB-1. Northern blot analysis revealed that YB-1 mRNA was present in all human tissues examined. Rabbit antibodies were generated against synthetic peptides corresponding to YB-1, and indirect immunofluorescence microscopy with these antibodies showed that the concentration of YB-1 in all cisplatin-resistant cell lines examined was higher than that in the respective drug-sensitive parental cells. Transfection of human epidermoid cancer KB cells with a YB-1 antisense construct established two cell lines with reduced concentrations of YB-1. These transfectants showed increased sensitivity to cisplatin, mitomycin C, and UV radiation but not to vincristine, doxorubicin, camptothecin, or etoposide. Thus, YB-1 may protect cells from the cytotoxic effects of agents that induce cross-linking of DNA, suggesting a novel function of this ancestor DNA-binding protein.

Amino Acid Sequence↗
PubMed1996

A transcranial doppler ultrasonography study of cerebrovascular CO2 reactivity in mitochondrial encephalomyopathy.

BACKGROUND AND PURPOSE: To elucidate the pathogenic role of vascular involvement such as mitochondrial angiopathy in patients with mitochondrial encephalomyopathy (MEM). we used the transcranial Doppler sonography (TCD) method to detect impairment of cerebrovascular CO2 reactivity. METHODS: The cerebral perfusion reserve in 13 MEM patients, including 6 with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) was studied by TCD for different CO2 partial pressures. For the parameter of mean flow velocity, the mean spatial Doppler frequency (fm) was obtained from the right and left middle cerebral arteries and basilar artery under conditions of normocapnia, hypercapnia, and hypocapnia in cases in which hyperventilation was possible. By fitting the obtained fm and the end-tidal CO2 partial pressure (PETCO2) to the exponential formula fm = a x e(K < PETCO2), where a is the theoretical fm at a PETCO2 of 0 mm Hg, the parameter K, an index of CO2 reactivity, was calculated. RESULTS: The K value was lower than control values at at least one site of the middle cerebral arteries and basilar artery of all patients with MELAS as well as the other MEM patients except for one patient with myoclonic epilepsy with ragged-red fiber and one with Kearns-Sayer syndrome. CONCLUSIONS: Our results suggest that there is a high incidence of impairment of cerebrovascular CO2 reactivity in MEM patients. Moreover, the noninvasive TCD method was found useful for evaluation of cerebral hemodynamics in MEM patients.

Adolescent↗
PubMed1996

[SPECT, MRI and EEG in infants with lissencephaly].

Single photon emission tomography (SPECT), MRI and EEG were studied in two infants with lissencephaly. One infant had generalized tonic convulsions at 7 month of age and continuous high voltage fast activities on EEG. The other infant developed infantile spasms at the age of 2.5 months, and showed low voltage disorganized background with pseudorhythmic high voltage sharp waves on EEG. Cranial CT and MRI in both infants revealed abnormally thick cortex, dilatation of the lateral ventricles, and smooth or relatively smooth cerebral surface. In SPECT studies, a diffuse increase of tracer uptake was shown at the cerebral cortex compared with the basal ganglia or cerebellum in both infants. The SPECT finding might reflect the abnormal cortical architectures in this cerebral malformation.

Brain↗
PubMed1996

[Endoscopic mucosal resection for early gastric cancer].

UNLABELLED: Endoscopic therapy of gastric cancer has been mainly performed to early cancer of nonresectable cases, for example patients having severe complications, high aged group and patients refusing the operation. Recently, endoscopic mucosal resection (EMR) made it possible to do radical resection for small gastric cancer of resectable cases. 112 patients of small cancers which diagnosed as a cancer limited to the mucosa were investigated. Indication to perform EMR instead of surgery were determined pathologically as follows, 1. depressed type of cancer not accompanying with converging folds measuring 1 cm or less in size, 2. elevated type of cancer measuring 2 cm or less in size, 3. differentiated type of carcinomas. According to those indications, 112 cases with 129 lesions of early gastric cancer were resected. The incision procedure consisted in EMR using two-channel fiberscope, a large chating forceps and a snare, the tissue being ablated with a high frequency electrical current. 2-6 ml of phisocal saline was locally infused at the submucosal level before resection to do it safely. RESULTS: Relationship between the prognosis and the histological distance from the edge of the specimen to the margin of the cancer were discussed. All of 81 cases having the distance more than 2 mm, it's called 'complete radical resection', were not recurrent, on the other hand 4 of 24 cases having the distance less than 2 mm, called 'incomplete radical resection', were recurrent at the site of resection and 12 of 24 cases obviously cancer spread to the edge of the specimen, called 'non-radical resection', were recognized the recurrence. conclusion, 1) On endoscopical resection for small gastric cancer, the distance more than 2 mm between the edge of the specimen and the margin of the cancer was necessary to get a complete radical resection. 2) Technical and mechanical problems still remained at the case of the cancer located in the angular region and gastric body.

Endoscopy↗
PubMed1995

Modulation by bovine angiogenin of tubular morphogenesis and expression of plasminogen activator in bovine endothelial cells.

Angiogenin is a potent angiogenic molecule in the chick chorioallantoic membrane assay and rabbit corneal assay. However, no angiogenic activity has been reported in in vitro system. In this study, we isolated and purified angiogenin from bovine milk, and the biological effect of the bovine angiogenin on bovine endothelial cells was examined in in vitro angiogenesis models. Bovine angiogenin significantly stimulated both cell migration and formation of tube-like structures in the collagen gel by bovine aortic endothelial cells. Angiogenin at 10-100 ng/ml stimulated about 2-fold higher the tube formation when basic fibroblast growth factor (bFGF) at 10 ng/ml stimulated about 3-fold over the control. Tubular morphogenesis stimulated by bFGF or angiogenin was almost completely blocked in the presence of aprotinin, an inhibitor of serine proteases. Angiogenin up-regulated both mRNA level and activity of urokinase type plasminogen activator, a key mediator of angiogenesis. Moreover, both bFGF and bovine angiogenin induced a marked increase of c-fos mRNA level at 30 min after stimulation. These novel effects of bovine angiogenin are to be discussed in relation to its structure specificity.

Allantois↗
PubMed1995

Interaction between valproate formulation and phenytoin concentrations.

Changes in phenytoin concentrations caused by switching valproate formulations with different absorption rates were retrospectively investigated in eleven epileptic patients receiving treatment with both drugs. Total plasma phenytoin concentrations were measured before and after a standard tablet of valproate was replaced by the same dose as a slow-release tablet. The mean plasma phenytoin level rose significantly from 14.4 to 18.7 micrograms.ml-1. Nine of eleven patients had markedly increased phenytoin levels (by 21 to 72%), and two developed toxic symptoms. The results indicate that changing valproate formulations can cause major alterations in the plasma concentration of co-administered phenytoin.

Adolescent↗
PubMed1995

Regenerative capacity of mdx mouse muscles after repeated applications of myo-necrotic bupivacaine.

We injected bupivacaine (BPVC), which produces muscle fiber necrosis, repeatedly into the soleus muscles of mdx mice, which represent a model of human Duchenne muscular dystrophy, over a 12-month period. Cytological and morphometric analysis revealed that the regenerative capacity of repeatedly BPVC-injected mdx muscles was almost equal to that of the saline-injected mdx muscles. At 9 months of age the endomysial collagen content of mdx muscles was 4.6 times that of control mice muscles, and was 7.2 times that of control mice muscle at 12 months. These results suggest that the regenerative capacity of the mdx muscle is quite large and that myo-necrosis induced by an extrinsic cause, such as BPVC, may not be an important factor in the disease progress. However, endomysial collagen, for which the mechanism of increase may be related to the defect of dystrophin, may play an important role in gradual decline of regeneration.

Age Factors↗
PubMed1994

Newly discovered photodegradation products of nifedipine in hospital prescriptions.

New photodegradation products of nifedipine (1) have been isolated. They were found in tablets dispensed in the pulverized form by hospitals. 1 decomposed concurrently into six components after storage of 30 days under exposure to normal room light. The main photoproduct was a nitroso derivative (2) and others were minor. Preparative thin-layer chromatography has been used to isolate the six photodegradation products. The chemical structures of these isolated compounds were identified or estimated by comparison with authentic samples and/or using UV, IR, 1H NMR, mass spectroscopy, melting point determination, and elementary analysis. From these analyses, it was found that 1 was converted into a cis-azoxy derivative (4), a trans-azoxy derivative (5), a N,N'-dioxide derivative (6) and a lactam derivative (7) in addition to 2 and a nitro derivative (3). Furthermore, it is proposed that 2 is mainly responsible for the formation of these new products (4-7) by photochemical condensation.

Chromatography, High Pressure Liquid↗
PubMed1993

[Manifesting carriers of Duchenne muscular dystrophy over two generations].

We report a family with manifesting DMD carriers over two generations. Sixty years old female (case 1) suffered from slowly progressive weakness since her thirties. Her youngest daughter aged 30 (case 2) had cramping calf muscle pain since her 5 years old. Progressive muscle weakness developed and lost her ambulation by the age of 20. Grandson of case 1 (son of case 1's eldest daughter who has no clinical symptoms) was diagnosed as DMD with deletion of exon 19-21 in dystrophin gene. Case 1 and case 2 were revealed to be DMD carriers. We speculate that, in this family, X-inactivation process was not random and paternal X was preferentially inactivated by maternal mutant X.

Adult↗
PubMed1992

Reversion of thyrotoxic atrial fibrillation in hypothyroid state after radioiodine treatment.

Twenty patients with thyrotoxic Basedow's disease complicated by atrial fibrillation lasting more than one month despite treatment with antithyroidal drugs were treated with radioiodine supplemented with an antithyroidal drug or inorganic iodine. We classified the 20 patients on the basis of atrial fibrillation reversion into two groups, one with reversion (group I) and the other without reversion (group II). In all 12 patients in group I, T4 and T3 decreased to hypothyroid levels in 3.2 +/- 1.3 months, and one month later all patients had their sinus rhythm restored while T4 and T3 remained below normal (2.6 +/- 1.1 micrograms/dl and 77.9 +/- 34.4 ng/dl, respectively). Although T4 and T3 also decreased within 3.5 +/- 1.8 months in all 8 patients in group II, one month later, atrial fibrillation persisted while T4 and T3 (10.4 +/- 5.3 micrograms/dl and 157.7 +/- 67.5 ng/dl, respectively) rose significantly compared to those in group I (P less than 0.001 and P less than 0.01, respectively). For reversion of atrial fibrillation it is important that the onset of hypothyroidism is rapidly induced by radioiodine and that hypothyroidism continues for at least one month.

Adult↗