Biomedical subjects
T Iwata
Publications and source records attributed to T Iwata.
Chlorpromazine induces population increase of synaptic vesicles in the rat hypothalamic ventromedial nucleus.
The population of synaptic vesicles per synaptic area in the hypothalamic ventromedial nucleus of rats treated with chlorpromazine (CP) for 3 days was compared with that of controls. In type I synapse, which contained 400-800 A small spherical vesicles (s-vesicles), together with 800-1200 A large spherical dense-cored vesicles (lc-vesicles), the population of s-vesicles increased 57.8% in the CP rats, In type II synapse, which contained only s-vesicles, the rate of increase among CP animals was 15.4%. Findings suggested that CP blocks the release of the vesicles from the presynaptic site or inhibits the transport function for biogenic amines through the presynaptic membrane, and type I synapse may be aminergic.
[Four cases of Morgagni diaphragmatic hernia operated successfully (author's transl)].
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Studies on steroids. CIX. O-omega-haloalkyloximes, new derivatives for gas chromatography-mass spectrometry of oxosteroids.
Several kinds of omega-haloalkoxyamines have been prepared as new derivative-forming agents applicable for the gas chromatography-mass spectrometry of carbonyl compounds. Of these reagents, 2-chloroethoxyamine hydrochloride [O-(2-chloroethyl)hydroxylamine] was the most suitable for use with oxosteroids because of its higher reactivity and the appropriate retention value and satisfactory chromatographic properties of the resulting oximes. The contribution to the retention value due to formation of the 2-chloroethyloxime was determined for 5alpha-androstanones having the oxo-group at various positions in the steroid nucleus. As expected, 17-oxosteroid O-2-haloethyloximes exhibit readily distinguishable isotope peaks as a cluster in the mas spectrum.
Frog lysozyme. I. Its identification, occurrence as isozymes, and quantitative distribution in tissues of the leopard frog, Rana pipiens.
In the course of examining the etiology of the Lucké renal adenocarcinoma of the frog, Rana pipiens, it was found that organs of the normal adult contain bacteriolytic enzymes. These enzymes all satisfied the six criteria for the identification of lysozymes and at least eight forms were separable by polyacrylamide gel electrophoresis. Their qualitative and quantitative distribution was organ-specific. All eight isozymes were found in normal kidney, while liver and spleen contained seven forms; skin, six; ovarian egg, five; and serum, two. In quantitative assays using a radial diffusion test, spleen had the greatest lysozyme concentration, followed in descending order by kidney, liver, skin, and ovary. Serum contained very low amounts. In terms of enzyme activity per animal, ovary was the highest ranking organ. As such a large number of lysozyme isozymes has not been reported in any other organism, their origins and functions are considered in the context of their presence in an ectotherm.
[Atypical mitochondria and crystallines in chromatolytic neuronal swelling].
Chromatolytic neuronal swelling was observed in the various brain regions, e. g. precentral cortex, pons and anterior horn of the spinal cord etc., of a 50-year-old woman showing psycho-organic syndrome and various neurological symptoms over a period of 14 years. In these inflated, chromatolytic nerve cells, atypical mitochondrias and paracrystalline structures were seen. Atypical mitochondrias contained membranous trans-somal bridges composed of about 60 A parallel filaments with a spacing of about 80 A. Paracystalline structures consisted of 7-16 hexagonal lattices with electron-light dots 160 A in diameter and with 280 A spacing. The goniometer revealed another featue of the paracrystals, i.e., lamellar structures consisting of 4-10 parallel filaments 120 A thick with a spacing of 160 A. These paracrystals were compared with similar structures in physiological and pathological conditions and the significance of the atypical mitochondrias was discussed.
[Antiepileptic activity of clonazepam--an antiepileptic benzodiazepine derivative].
Clonazepam, an antiepileptic benzodiazepine derivative was administered into 30 patients mainly with incurable type epilepsy. Results were as summarized below: (1) Clonazepam was effective in 44.4% of 36 cases of seizures. The initial effect was noticed in 55.6%. (2) Clonazepam was proved to have a broad spectrum in its efficacy. It showed the highest rate of effectiveness, 71.4%, on psychomotor seizures. (3) Clonazepam was effective in all 4 cases of the photogenic epilepsy which shows the photosensitivity in the EEG. With the exception of 1 case, the sensitivity in the EEG also disappeared responding to clonazepam. (4) The Jacksonian type of the partial motor seizure disappeared in 2 cases after the administration with clonazepam. (5) The effects of clonazepam of EEG were examined in 24 patients. The abnormality of the basic activity, the diffuse epileptic discharge and the focal epileptic discharge were improved in 29.2%, 61.5% and 66.7%, respectively. In addition, the rate of the clinical effectiveness was high in the cases with the centrencephalic discharge. (6) Side effects were observed to have appeared in 38.9% of the patients. They were mostly drowsiness and ataxia. (7) Based on the above-mentioned results, it can be claimed that clonazepam is effective on psychomotor seizures, photogenic epilepsy and the secondary type of generalized convulsion (Jacksonian).
The fine structural localization of peroxidase activity in goblet cells of the conjunctival epithelium of rats.
Cytochemical investigation of peroxidase was made on the conjunctival goblet cells, using the diaminobenzidine method. Many goblet cells in the conjunctiva demonstrated this reaction. The reaction was present in secretory granules as well as in the perinuclear cisterna, the rough endoplasmic reticulum, several Golgi saccules and adjacent small smooth-surfaced vesicles, and condensing vacuoles. Each secretory granule within a goblet cell showed a different degree of reaction, hence it is concluded that some goblet cells probably produce both mucous substance and peroxidase in one cell. The mode of production of peroxidase in goblet cells is concluded to be similar to that of secretory proteins in pancreatic exocrine cells. The enzyme, together with thiocyanate and endogenous hydrogen peroxide, is thought to serve as an anti-infectious agent in tears.
Cytochemical studies on endogenous peroxidase in conjunctival and corneal epithelial cells.
Endogenous peroxidase activity in conjunctival and corneal epithelial cells was studied cytochemically by the diaminobenzidine method. Many peroxidase-positive cells were found in the fornical conjunctiva. They were also seen, but less frequently, in the tarsal conjunctiva, limbus, and cornea. Three types of peroxidase-positive (cytochemically reactive) cells were differentiated besides goblet cells: (1) the most superficial cells with several reactive secretory granules (2) moth-eaten cells near the surface with abundant reactive microgranules, and (3) deeper cells with reactive microgranules and a few densely reactive granules. Some goblet cells shared the same characteristics with other types of cells. The relationship among these cells, functional differences between granules, and the function of peroxidase are discussed.
Stereochemistry, metabolism, and antitumor activity of 4-hydroperoxyisophosphamide (NSC-227114) and its stereoisomer.
An acid-catalyzed isomerization of 4-hydroperoxyisophosphamide, a synthetic compound with potential antitumor activity, produced a new crystalline epimer having an inverted stereochemistry at the phosphorus atom. The stereochemistry of these epimeric hydroperoxides is discussed on the basis of their chemical and nuclear magnetic resonance properties. The epimers show essentially the same metabolic behavior. This behavior is, however, different from that of isophosphamide (IP) which is metabolized in part via pathways ineffective for its activation. The newly isolated epimer shows slightly higher activity against some kinds of experimental tumors than the original hydroperoxide, suggesting that the inverted stereochemistry of the alkylating group at the phosphorus atom is effective in promoting the antitumor activity of the activated species of IP.
Studies on steroids. III. A new type of derivative for electron capture-gas chromatography of ketosteroids.
Pentafluorobenzyloxyamine is presented as a new derivatizing agent for gas chromatography of ketones using electron capture detection. The typical 17-ketosteroid was readily transformed into the O-pentafluorobenzyloxime which on usual trimethylsilylation led to a 3-trimethylsilyl ether derivative exhibiting good gas chromatographic properties. The derivatization procedure was applied to the determination of dehydroepiandrosterone in human plasma by electron capture-gas chromatography employing an internal standard method and in consequence satisfactory results were obtained.
Studies on cyclophosphamide metabolites and their related compounds. 2. Preparation of an active species of cyclophosphamide and related compounds.
A synthetic study was made on the active metabolite of cyclophosphamide. Ozonolysis of O-(3 butenyl)-N,N-bis(2-chloroethyl)phosphorodiamidate, prepared by reaction of POC13 with 3-buten-1-ol followed by treatment with N,N-bis(2-chloroethyl)amine (nor mustard) and NH3, afforded 2-[bis(2-chloroethyl)amino]-4-hydroperoxytetrahydro-2H-1, 3,2-oxazaphosphorine 2-oxide (4-hydroperoxycyclophosphamide). Deoxygenation of 4-hydroperoxycyclophosphamide by triphenylphosphine yielded 4-hydroxycyclophosphamide in a pure crystalline state. These products exhibited high cytostatic activity in both in vitro and in vivo experiments. The results give confirmatory evidence for the hypothesis that C4-hydroxylation on the 1,3,2-oxazaphosphorinane ring of cyclophosphamide is necessary for its activation.
[Urinary beta-2-microglobulin level of the inhabitants in cadmium polluted districts].
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New derivatives for the gas chromatographic resolution of amino acid enantiomers.
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Synthesis and metabolic behavior of the suggested active species of isophosphamide having cytostatic activity.
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Probing a Membrane Matrix Regulating Hormone Action: II. The Kinetics of Lipid-Induced Growth and Ethylene Production.
Lipids which are active oleanimins, i.e., those which stimulate respiration and auxin-induced cell elongation of pea stem sections, also initiate a period of ethylene formation in them after a lag period of at least 1 hour. Production of ethylene requires auxin, is inhibited by cycloheximide and dinitrophenol applied during or before the lag period, and is greatly stimulated by lipids longer than 20 Angstroms in length such as heptadecyl-benzene, chloro- or iodohexadecane, triolein, and vitamins E and K(1), but not by the shorter chloro- and iododecane. beta-Stigmasterol at 10 to 40 mum concentrations depresses both oleanimin-induced growth and ethylene formation.The effect of oleanimins on the growth rate steadily declines and disappears after 6 hours, whereas oleanimin induction of ethylene stays at a high level until it rapidly disappears after 6 hours. Nongrowing second internode sections also produce ethylene on oleanimin treatment, so ethylene formation is not dependent on cell elongation even though it requires auxin. Preincubation with heptadecylbenzene or auxin does not change the delay of an hour or more before ethylene is produced, whereas increases in growth are noted at the earliest measurements. Oleanimins stimulate growth at less than optimal auxin concentration, even as low as 20 nm, where a proportional ethylene formation is not noted. It is concluded that ethylene formation is not causally related to growth in these tissues.The decline in oleanimin-induced ethylene formation is not changed by renewal of the incubation medium, and sucrose which is required to maintain growth for 20 hours does not influence growth or ethylene formation up to 6 hours. l-Methionine increases ethylene formed after heptadecylbenzene treatment, but unexpectedly, malonate is much more effective.Auxin concentrations supraoptimal for growth cause no growth rate reductions for the first 10 hours, but they greatly enhance oleanimin-induced ethylene formation even when heptadecylbenzene is added after 6 hours. Applied ethylene even at concentrations much above those produced by the tissue itself fails to stimulate or inhibit short term pea stem section growth. It is concluded that the effect of oleanmins on growth is not mediated by ethylene. The similarities in concentration and molecular dimensions of these structurally diverse lipids which simultaneously stimulate respiration, growth, and ethylene formation, suggest a single site of action located in a regulatory membrane.
Relapsing polychondritis--report of a case with ultrastructural findings of the ear cartilage.
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[Gas-chromatography of steroid metabolites].
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