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Biomedical subjects

R Kuroda

Publications and source records attributed to R Kuroda.

At least 127 records · Page 7Linked to original sources
PubMed1989

[Neurofunctional disturbances as related to cortical ischemia and white matter ischemia].

We evaluated regional cerebral blood flow (rCBF) by means of hydrogen clearance method as well as [14C]-iodoantipyrine autoradiographic method, cortical auditory evoked potentials (AEP), somatosensory evoked potentials (SEP) induced by forelimb (median nerve) stimulation (SEP-F), and SEP induced by hindlimb (tibial nerve) stimulation (SEP-H) in cats after occlusion of the left middle cerebral artery (MCA) under alpha-chloralose anesthesia. According to the degree of ischemia, the experimental animals were divided into two groups. One was the critical ischemia which was defined as permanent total suppression of AEP, and low residual blood flow in the auditory cortex. And the other was the non-critical ischemia which included transient suppression and spontaneous recovery of the cortical sensory evoked potentials, and high residual blood flow (greater than 15 ml/100 g/min). In one cat with transient suppression of three kinds of sensory evoked potentials, the [14C]-iodoantipyrine (IAP) autoradiograph revealed only a limited ischemic area of subcortical white matter. In the critical ischemia group, ischemia of the primary sensory cortex ranged from the mostly affected primary auditory cortex (supplied by the MCA) to the least affected hindlimb projection area within primary somatosensory cortex (supplied by the ACA). The forelimb projection area of the primary somatosensory cortex (supplied by both ACA and MCA) showed a mild or moderate reduction of rCBF after occlusion. The [14C]-IAP autoradiograph showed severe reduction of the white matter including the somatosensory pathway in the wide range. However, rCBF in the thalamus and hindlimb projection area within somatosensory cortex was almost intact in the cat with ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Growth activity of meningeal carcinomatosis--immunohistochemical study using anti-BrdU monoclonal antibody].

We have developed an experimental model of leptomeningeal tumor by inoculating Walker 256 carcinosarcoma cells into the cisterna magna of rats. This model was considered to be useful in studying pathophysiology and treatment of malignant brain tumors. In this study, the growth kinetics of this experimental tumor was investigated by using the immunohistochemical technique with an anti-BrdU monoclonal antibody. Walker 256 carcinosarcoma was subcutaneously passaged in female Wistar rats. Seven days after subcutaneous inoculation, the tumor was aseptically removed and minced in Hank's medium by scissors to make single cell suspension of the tumor. The cell suspension was adjusted to 1 x 10(5) cells/ml. And 0.1 ml was inoculated percutaneously into the cisterna magna of female Wistar rats weighing 150 gr. Every day after tumor inoculation, the animal (5 on each day) was sacrificed 30 minutes after intravenous BrdU (200 mg/kg) and perfused by saline. Then, the brain was removed, fixed in ethanol and embedded in paraffin. Coronal sections of the brain 6 mu in thickness were cut and stained by the indirect immunoperoxidase (ABC) method. The anti-BrdU monoclonal antibody (Becton-Dickinson) was diluted in 1:100. The sections were counterstained by hematoxylin. Labelling index (L.I.) of the tumor was obtained by counting immunoreactive cells under the microscope. L.I. of the subcutaneous tumor 7 days after inoculation was 52.4%. In the tumor 1 to 3 days after inoculation, L.I. was still low and between 11.9 and 15.1%. Four or 5 days after inoculation, the tumor cells grew in several layers in the subarachnoid space. L.I. at this stage of the tumor growth was 26.6 to 34.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Crystallographic and molecular mechanics calculations on the anti-tumor drugs N-[(2-dimethylamino)ethyl]-and N-[(2-dimethyl-amino)butyl]-9-aminoacridine-4-carboxamides and their dications: implications for models of DNA-binding.

The molecular structures of the N-(2-dimethylamino)ethyl and N-(2-dimethylamino)butyl derivatives of 9-aminoacridine-4-carboxamide, of current interest as potential anti-cancer agents have been determined by X-ray Crystallography. Both are in the free base form and have an intramolecular-hydrogen bond between N10 of the acridine and the nitrogen atom of the carboxamide substituent. Molecular mechanics calculations have been used to explore the conformational flexibility of this substituent with respect to the chromophore in order to determine the low-energy conformers of both free base and protonated forms. These have revealed flexibility in the system with relatively low energy cost, especially in the physiological condition when the N10 atom is protonated and suggest that a previously published model for the interaction of these compounds with DNA, is energetically feasible. Implications for interactions with DNA have also been examined by computer modelling.

Aminoacridines↗
PubMed1987

Experimental anatomical considerations of the dorsal root entry zone lesions for pain relief.

Dorsal root entry zone (DREZ) lesions were made in the cervical dorsal horn in cat and monkey. Terminal degeneration was observed in the lateral cervical nucleus in cat and contralateral VPL in monkey by Fink-Heimer stain. WGA-HRP was injected in the cervical dorsal horn of cat and retrograde labelled cells were observed mainly in the raphe nucleus, parabrachial nucleus, locus coeruleus, Kölliker-Fuse nucleus, Eddinger-Westphal nucleus, and hypothalamic area, indicating that these descending fiber systems are involved by the DREZ lesion. The functional role of these fibers in regard to deafferentation pain relief seems now to be open to discussion.

Animals↗
PubMed1986

Synthesis and estrogen receptor binding of 6,7-dihydro-8-phenyl-9-[4-[2-(dimethylamino)ethoxy] phenyl]-5H-benzocycloheptene, a nonisomerizable analogue of tamoxifen. X-ray crystallographic studies.

Syntheses of the title compound (5), a novel nonisomerizable antiestrogen containing a seven-membered ring, are described. In one method, 6,7-dihydro-9-(4-methoxyphenyl)-5H-benzocycloheptene was brominated at the 8-position and the bromine displaced by phenylzinc chloride with palladium complex catalysis to introduce the 8-phenyl substituent. Alternatively, benzosuberone was alpha phenylated with tricarbonyl(eta 6-fluorobenzene)chromium (0) and the product treated with the appropriate aryllithium reagent to introduce the 9-aryl group last. The relative binding affinities for estrogen receptors in cell cytosol and whole cells and growth inhibitory activity against the MCF-7 human breast tumor cell line in vitro were for 5 comparable to those of tamoxifen (1) and the corresponding six-membered ring analogue (7). X-ray crystallographic analyses of 10 and 15, which are methoxy derivatives of 5 and 7, show that in some respects 5 bears a closer structural relationship to tamoxifen than does nafoxidine (3) or 7. Thus, the aromatic ring, which is fused in the cyclic analogues, was twisted 64, 45, 20, and 19 degrees out of the plane of the double bond for 1, 10, 3, and 15, respectively. Low-temperature NMR studies indicate that 5 is more rigid than tamoxifen; interconversion between enantiomeric conformers is slow on the NMR time scale at -75 degrees C.

Animals↗
PubMed1985

Interaction of bleomycin A2 with deoxyribonucleic acid: DNA unwinding and inhibition of bleomycin-induced DNA breakage by cationic thiazole amides related to bleomycin A2.

The association of the antitumor antibiotic bleomycin A2 with DNA has been investigated by employing several 2-substituted thiazole-4-carboxamides, structurally related to the cationic terminus of the drug. With a 5'-32P-labeled DNA restriction fragment from plasmid pBR322 as substrate, these compounds have been shown to inhibit bleomycin-induced DNA breakage. Analogues possessing 2'-aromatic substituents on the bithiazole ring were more potent inhibitors than those carrying 2'-aliphatic groups, e.g., the acetyl dipeptide A2. The degree of inhibition was similar at all scission sites on DNA, and inclusion of the analogues did not induce bleomycin cleavage at new sites. DNA binding of bithiazole derivatives has also been studied by two complementary topological methods. Two-dimensional gel electrophoresis using a population of DNA topoisomers and DNA relaxation experiments involving calf thymus DNA topoisomerase I and pBR322 DNA reveal that bleomycin bithiazole analogues unwind closed circular duplex DNA. The inhibition and unwinding studies together support recent NMR studies suggesting that both bleomycin A2 and synthetic bithiazole derivatives bind to DNA by an intercalative mechanism. The results are discussed in relation to the DNA breakage properties of bleomycin A2.

Animals↗
PubMed1985

Comparative studies of the metabolic activation of chrysene in rodent and human skin.

Metabolism and activation of chrysene was examined in mouse, rat and human skin using a short-term organ culture technique. Mouse skin released larger quantities of free dihydrodiols into the culture medium than either rat or human skin and greater quantities of chrysene metabolites became covalently bound to the DNA of mouse skin. The stereochemistry of the chrysene-1,2-diol that was formed by each skin type was examined using high-performance liquid chromatography (HPLC) with a chiral stationary phase to resolve the enantiomers. It was found that in each case the (-)-enantiomer predominated. When hydrolysates of DNA extracted from rodent or human skin that had been treated with 3H-labelled chrysene were chromatographed on Sephadex LH-20 columns, the elution profiles of the hydrocarbon-DNA adducts were found to vary between the species studied. Further examination using HPLC showed that some of the adducts formed in skin had the chromatographic characteristics of adducts formed when the anti-isomer of the 'bay-region' diol-epoxide of chrysene (r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene) reacted with DNA and that others had the characteristics of triol-epoxide adducts.

Animals↗
PubMed1985

Structural studies on some tamoxifen derivatives.

The crystal structures of four derivatives of the antiestrogenic drug tamoxifen are described. These are of 2-hydroxy-, 3-hydroxy-, and 2-methyl-4-hydroxytamoxifen and of 1-(4-methoxyphenyl)-2-phenyl-1-[(tetrahydropyran-2-yloxy)phenyl]-1 -butanol, the synthetic precursor to 2-hydroxytamoxifen. All compounds have trans stereochemistry about the ethylene double bond, as in tamoxifen itself. The orientations of the hydroxy substituents have been found to differ by 180 degrees, depending on the nature of the compound. Empirical energy calculations have been used to show that the barrier to free rotation for the hydroxy-substituted phenyl rings is too high for interconversion to take place. These orientational differences are, it is suggested, related to the marked differences in estrogen receptor binding ability.

Crystallography↗
PubMed1985

Clinicoanatomical study of thalamic stimulation for pain relief.

Our small experiences with electrical stimulation in the VPL and VPM for dysesthetic pain show that it provoked only paresthesia and induced some relief of pain. It does not increase the beta-endorphin level in CSF. To clarify the anatomical substrata in VPL stimulation, neuroanatomical studies were done about the inputs to VPL in man, monkey and cat by the Fink-Heimer method. The spinothalamic tract terminates in VPL in a patchy fashion in the monkey. The corticothalamic fibers from SI and SII cortex project to VPL and VPM in somatotopical organization in the cat. SI and SII cortices have reciprocal connections, in addition to projections to area 5 or SIII cortex. The corticofugal fibers to the magnocellular and gigantocellular tegmental fields are suggested in addition to the dorsal column nuclei, spinal trigeminal nuclei and spinal posterior horn in cat. The medial lemniscus input to VPL and the above neural circuits are thought to be associated with VPL stimulation.

Animals↗
PubMed1984

Studies on the conformation and dynamics of the C8-substituted guanine adduct of the carcinogen acetylaminofluorene; model for a possible Z-DNA modified structure.

The structure of an adduct between guanine and the carcinogen acetylaminofluorene has been examined in the solid state by X-ray crystallography, and in solution by NMR techniques. The observed conformations have been compared with predictions from energy calculations and their relevance to models of adducts with DNA has been examined.

2-Acetylaminofluorene↗
PubMed1984

X-ray and NMR studies of trans-dihydroxo-platinum(IV) antitumor complexes.

Products from oxidative-addition reactions of H2O2 with cis-diamineplatinum(II) complexes have been studied by NMR and X-ray crystallography. Reaction of H2O2 with cis-diamminemalonatoplatinum(II) gave one product which was shown by X-ray crystallography to be the trans-dihydroxoplatinum(IV) complex: trans-dihydroxo-cis-diamminemalonatoplatinum(IV) dihydrate, compound 1, triclinic, space group P1, a = 6.275, b = 8.801, c = 9.621 A, alpha = 106.73, beta = 107.17, gamma = 67.67 degrees. In contrast, reactions of H2O2 with the related 1,1-cyclobutanedicarboxylato and ethylmalonato-platinum(II) complexes gave two Pt(IV) products each with similar 195Pt chemical shifts (ca. 50 ppm apart) but different 1J(195Pt-14N) couplings of ca. 205 and 229 Hz. It is suggested that the different course of reaction for these complexes is related to destabilization of the boat conformation of the chelate ring in hydroxoplatinum(IV) complexes containing substituted malonates as shown by empirical energy calculations. The crystal structures of two other related Pt(IV) complexes are reported: cis-dichloro-trans-dihydroxo-cis-bis(methylamine)platinum(IV) tetrahydrate, compound 2, monoclinic, space group C2/c, a = 17.746, b = 7.460 and c = 9.248 A, beta = 94.33 degrees, and cis-dichloro-trans-dihydroxo-cis-bis(3-methoxy-n-propylamine)pl Platinum(IV), compound 3, triclinic, space group P1, a = 7.559, b = 8.407, c = 13.168 A, alpha = 105.57, beta = 105.50, gamma = 93.05 degrees. All coordination geometries were closely octahedral and there were extensive three-dimensional hydrogen-bonding networks in the crystals involving amine NH, OH, Cl, or carboxylate O, and lattice H2O.

Antineoplastic Agents↗
PubMed1983

The cells of origin of cat trigeminothalamic projections: especially in the caudal medulla.

Thalamic projections from the caudal medulla of the cat were examined using the method of retrograde axonal transport of horseradish peroxidase (HRP). Injections were made unilaterally in various thalamic regions. Large injections labeled cells in the subnuclei: zonalis (Vcz), gelatinosus (Vcg), magnocellularis (Vcm), reticularis dorsalis (Vcrd) and ventralis (Vcv) medullae oblongatae. The largest number of labeled cells were in Vcz, Vcrd and Vcrv. Most of the labeled cells in Vcz and Vcrd were contralateral to the injection site, although the labeled cells in the Vcrv were bilateral. Small injections were made into the medial, lateral and dorsal regions of the nucleus ventralis posteromedialis (VPM), rostral regions of the posterior nuclei (POm and PO1), caudal POm, the nucleus centralis lateralis (CL) and the center median-parafascicular nuclear complex (CM-Pf). Most of the neurons in Vcz were found to project to the medial VPM and some to the caudal POm. A small number of cells in the Vcrd project to the medial VPM, but a large number project to the caudal POm and CM-Pf complex. The largest number of neurons projecting to the CM-Pf complex was present in Vcrv, where the labeled cells were bilateral. The types of trigeminothalamic projecting cells and the sizes of their somata were observed for different subnuclei and a considerable difference was found to exist among the subnuclei. This anatomical differentiation of the trigeminothalamic projections probably reflects a functional specialization of neuronal location since the functional properties of neurons vary according to their locations.

Animals↗
PubMed1983

The antitumor complex ethylenediamine platinum (II) malonate: x-ray structure analysis, and studies of its stability in solution.

The anti-tumour compound ethylenediamine platinum (II) malonate has been examined by x-ray crystallography. The molecular structure has a square-planar arrangement around the platinum atom, with the malonate group in a boat conformation and cis to the ethylenediamine group. Solution studies have shown that the malonate ion may be readily displaced from the complex, especially by chloride ion, and at low pH. The implications of this finding for in vivo drug administration are discussed.

Antineoplastic Agents↗