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Biomedical subjects

T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 487 records · Page 27Linked to original sources
PubMed1991

Novel cerebroprotective agents with central nervous system stimulating activity. 2. Synthesis and pharmacology of the 1-(acylamino)-7-hydroxyindan derivatives.

In a continuous search for a novel cerebroprotective drug with a central nervous system (CNS) stimulating activity, a series of 1-(acylamino)-7-hydroxyindan derivatives has been synthesized and tested for its dual activities. The cerebroprotective activities of the compounds in this series were evaluated in terms of their effect on the survival of mice in hypoxic conditions (210 mmHg), and their CNS stimulating activities were examined by evaluating their promotional effects on the recovery from coma induced by cerebral concussion in mice. Several compounds prolonged the survival of mice in the hypoxic conditions at a dose of 30 mg/kg po. Four compounds in this series showed the CNS-stimulating effect at the same dose. Among them, 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetyl]amino]-2,2,4, 6-tetramethylindan (18, OPC-14117), which was active in the two tests with no side effect up to 500 mg/kg po daily for 2 weeks of administration to rats, was selected for preclinical investigations.

Animals↗
PubMed1991

Platelet aggregation inhibitors from the seeds of Swietenia mahagoni: inhibition of in vitro and in vivo platelet-activating factor-induced effects of tetranortriterpenoids related to swietenine and swietenolide.

The ether extract from the seeds of Swietenia mahagoni Jacq. (Meliaceae) was found to inhibit platelet-activating factor (PAF)-induced platelet aggregation. Systematic separation of the extract afforded twenty eight tetranortriterpenoids related to swietenine and swietenolide. Among them, several new compounds, named swietemahonin A, D, E, and G and 3-O-acetylswietenolide and 6-O-acetylswietenolide, showed a strong inhibition against PAF-induced aggregation in vitro and in vivo assays.

Animals↗
PubMed1991

Cytological characteristics of human glioma-infiltrating lymphocytes stimulated with recombinant interleukin 2 and an anti-CD3 antibody.

Tumor-infiltrating lymphocytes (TIL) were generated from 10 glioma specimens by using recombinant interleukin-2 and an anti-CD3 antibody (CD3 + TILs). We obtained more than 1 x 10(9) cells in 5 cases, more than 5 x 10(8) cells in 2 cases, and about 1 x 10(8) cells in 3 cases during three weeks of incubation from small specimens ranging in weight from 0.5 to 2.0 g. In 4 cases, TILs were expanded following stimulation with only rIL-2 (CD3-TILs). The growth rate of CD3-TILs was less than that of CD3 + TILs. Cytotoxicity of CD3 + TILs was lower than that of lymphokine-activated killer (LAK) cells in a standard 4h 51Cr release assay. Cold target inhibition was undertaken in three cases and specific cytotoxicity could be shown in only one case. CD3 + TILs mainly consisted of CD3-positive cells, ranging from 63.2 to 99.9%. The ratio of CD4-positive cells to CD8-positive cells was not constant. The expression of Leu 7 and CD16 was low. The present study did not confirm previous findings that TILs were more tumor-selective and potent than LAK cells. Furthermore, the results on in vitro antitumor activity of those cells were not necessarily consistent with the results on their clinical activity. Further careful work is necessary on the preparation of immunocytes and the subsequent adoptive immunotherapy.

Adult↗
PubMed1991

Constituents of the roots of Boerhaavia diffusa L. III. Identification of Ca2+ channel antagonistic compound from the methanol extract.

Two known lignans, liriodendrin and syringaresinol mono-beta-D-glucoside, have been isolated from the methanol extract of the roots of Boerhaavia diffusa L. (Nyctaginaceae), and the former compound was found to exhibit a significant calcium (Ca2+) channel antagonistic effect in frog heart single cells using the whole-cell voltage clamp method. Reexamination of the carbon-13 nuclear magnetic resonance (13C-NMR) spectra of these compounds was also carried out by the use of two-dimensional NMR techniques including a 1H-detected heteronuclear multiple bond connectivity (HMBC) experiment, and it was found that the previous signal assignments for C-1' and C-4' have to be revised.

Animals↗
PubMed1991

Enzymatic sulfation of polyphenols related to tannins by arylsulfotransferase.

This report discusses a novel type of arylsulfotransferase (AST) which was derived from human intestinal bacterium sulfated polyphenolic compounds when p-nitrophenyl sulfate (PNS) was taken as a donor substrate. (+)-Catechin, (+/-)-catechin, (-)-epicatechin and (-)-epicatechin gallate were better substrates than tyramine. (-)-Epigallocatechin and (-)-epigallocatechin gallate were slightly worse substrates than tyramine. Although gallic acid was a bad substrate, alkyl gallate esters were better substrates than tyramine. The degree of acceptor specificity increased in proportion to the length of the alkyl group up to the carbon number of five. Pedunculagin, geraniin and corilagin were less effective than tyramine. Rosmarinic acid and penta-O-galloyl-beta-D-glucose were similarly well sulfated. Two products, 4'-monosulfate and 4',5-disulfate of (+)-catechin, were detected at a two-fold molar excess of PNS over (+)-catechin. When (+)-catechin-4'-monosulfate as an acceptor was enzymatically sulfated with PNS as a donor, only the 4',5-disulfate was produced. Thus, arylsulfotransferase was useful for the convenient preparation of sulfate esters of polyphenols at their specific hydroxyl groups.

Arylsulfotransferase↗
PubMed1991

Microtubule subunits of guinea pig vestibular epithelial cells.

Guinea pig cochlear supporting cells have microtubules which are composed of 15, instead of the ordinary 13, protofilaments. The microtubules form a large and stiff bundle involving abundant actin filaments to provide effective rigidity to the cell specialized for transduction of extremely high-frequent mechanical stimuli. We examined microtubules in guinea pig vestibular end organs with the transmission electron microscopy after treatment with tannic acid. Solitary microtubules occurred abundantly in the supranuclear region of type I hair cells, but sparsely in type II hair cells. Individual microtubules consisted of an ordinary set of 13 protofilaments in these hair cells as well as in the supporting cells. Supporting cells were characterized by cytoskeletal bundles of 2 to 30 microtubules which were found to be connected with actin filaments via cross-linking units. Results from the present investigation indicate that such less-organized microtubules of 13 protofilaments are sufficient for vestibular supporting cells which are specialized for detection of lower-frequency vibration together with fellow sensory cells.

Actins↗
PubMed1991

Microtubules of guinea pig cochlear epithelial cells.

By tannic acid staining, the 13-protofilament composition of cochlear hair cell microtubules, an impressive contrast against the 15-protofilament microtubules in cochlear pillar cells, was verified. The 15-protofilament microtubules formed a large and stiff cytoskeletal bundle in pillar cell bodies involving abundant actin filaments. The bundles were always situated vertically, i.e., longitudinally to the cell body axis, and were most numerous in the outer as well as the inner pillar cells in the basal turn, decreasing gradually toward the apex. Such gradient architecture of the pillar cell cytoskeleton can be correlated with the tuning mechanism for traveling waves of sound containing variable frequencies.

Animals↗
PubMed1991

Role of renomedullary thromboxane A2 in development of doca-salt hypertension.

To clarify the role of renal thromboxane (TX)A2 in the development of deoxycorticosterone acetate (DOCA)-salt induced hypertension, relationship between systolic blood pressure and the synthesis of renal TXA2 was investigated in 18 rats without and with OKY-046 administration which suppressed the synthesis of renal TXA2. Systolic blood pressure was significantly higher in DOCA-salt group than in control and OKY groups. The synthesis of 6-keto-prostaglandin(PG)F1 alpha and TXB2 in both renal arteries and cortical slices were more enhanced in DOCA-salt and OKY groups than in control group, but there was no significant difference between DOCA-salt and OKY groups. In contrast, the synthesis of 6-keto-PGF1 alpha in renomedullary slices did not vary significantly among three groups, and that of TXB2 was more increased in DOCA-salt group than in control and OKY groups. The cumulative sodium retention was significantly greater in DOCA-salt group than in control group. Administration of OKY-046 reduced the cumulative sodium retention in DOCA-salt rats by 45% toward that of the control group. These results might suggest that the enhanced production of renomedullary TXB2 was important to the development of DOCA-salt induced hypertension.

Animals↗
PubMed1991

Evaluation of superoxide scavenging activity of OPC-14117 by electron spin resonance technique.

OPC-14117 is a potent drug which has both brain function activating effect and protective effect against cerebral ischemia. Occurrences of these effects might be expected due to superoxide dismutase-like activity of OPC-14117. The present study has been conducted to evaluate the active oxygen scavenging activity of OPC-14117 and to explain the mechanisms of its pharmacological activities. The reaction of OPC-14117 and superoxide anion, generated in potassium superoxide, was examined by electron spin resonance technique at both liquid nitrogen (77 K) and room (22 degrees C) temperatures. OPC-14117 showed a higher superoxide scavenging activity than that of alpha-tocopherol in an aprotic solvent system. The active moiety of OPC-14117 to provide the scavenging effect was found due to the phenolic hydroxyl group of its indan skeleton.

Electron Spin Resonance Spectroscopy↗
PubMed1991

[Can fluorodeoxyglucose-positron emission tomography evaluate the functional differentiation of hepatocellular carcinoma].

Tumor uptake of 18F-fluorodeoxyglucose (FDG) was studied by dynamic positron emission tomography (PET) in 23 cases of hepatocellular carcinoma. The metabolic rate constants, K1 to K4, were generated by non-linear least square fitting method. We confirmed that K3 from the PET study significantly correlated with directly measured hexokinase activity of the cancer tissue. The region of HCC always had higher K3 values, which represents the hexokinase activity compared with the non-cancerous region. By FDG images, however, in 50% of cases the cancer region could not be clearly defined from the surrounding noncancerous hepatic tissue. These HCC cases without accumulation of FDG had a high ratio of K4/K3 (K4 represents glucose-6-phosphatase activity), which correlated well with the inverse ratio of FDG accumulating images on PET. According to the PET images which is represented by K4/K3 and the hexokinase activity which is represented by K3, we divided these 23 cases into three groups and retrospectively compared their survival rates. The groups with high K4/K3 (greater than or equal to 0.40) had longer survival than other groups. From the view point of glucose metabolism, the value of K4/K3 calculated from dynamic studies of FDG-PET may represent the functional differentiation of HCC.

Carcinoma, Hepatocellular↗
PubMed1991

[The effects of lowering of blood pressure on pain sensitivity in spontaneously hypertensive rats].

It has been reported that elevation of blood pressure produces a reduction in pain sensitivity. This study was designed to clarify the correlation in spontaneously hypertensive rats (SHR) between fall in blood pressure and pain sensitivity. In seven-weeks-old male SHR, the angiotensin converting inhibitor delapril (10 mg/kg/day) or calcium antagonist nifedipine (3 mg/kg/day) was administered orally every day for 8 weeks. Systolic blood pressure (SBP) pretreatment was significantly higher in the SHR than in normotensive Wistar-Kyoto (WKY) rats and pain sensitivity measured with the hot plate method was significantly lower in the SHR than in the WKY rats. Administration of both drugs produced a significant suppression of elevation of SBP, and produced a significant elevation of pain sensitivity. Furthermore, at 8 weeks after drug administration, urinary norepinephrine (UNE) significantly decreased and plasma beta-endorphin (beta-end) significantly increased. A significant correlation was noted between pain sensitivity and SBP and also between pain sensitivity and UNE. Of these, pain sensitivity was the more closely correlated to degree of change in UNE than to degree of change in SBP. It appears that elevation of pain sensitivity is due to suppression of the sympathetic nervous system by antihypertensive drugs, but not to elevation of beta-end levels. These data suggest that a fall in blood pressure through administration of delapril or nifedipine reverses decrease in pain sensitivity in SHR and that decrease in sympathetic tone plays an important role in the restoration of levels of sensitivity to pain.

Animals↗
PubMed1991

[Pseudoaneurysm of the extracranial vertebral artery; a case report].

Traumatic injury of the vertebral artery is rare and only a few reports have been presented. We treated a case of iatrogenic pseudoaneurysm of the extracranial vertebral artery. A 65-year-old man complained of headache and had a pulsating mass in the soft tissue of the neck which had continued for one month after evacuation of hypertensive cerebellar hemorrhage. The left VAG revealed a large pseudoaneurysm at the third portion of the vertebral artery and the right retrograde VAG revealed agenesis of the vertebral artery. To select the proper treatment was a dilemma. This case was treated by embolization using an occluding spring embolus with direct transcutaneous puncture of pseudoaneurysm. Following this treatment, the mass and associated symptoms resolved without neurological deficit.

Aged↗
PubMed1991

[Comparison of shape recovery ratios in various IOL haptics].

We examined shape recovery ratios of various IOL haptics (polypropylene, polyvinylidene fluoride, polymethylmethacrylate) under conditions resembling clinical use. Experiments were carried out using Ascon lens-holding forceps and compression tests in cylindrical holders. The experimental results indicated that PVDF haptics were superior to PP and 3-piece PMMA haptics. This would suggest the need for surgeons to establish safer implantation techniques in the future by taking into consideration the shape recovery characteristics of the haptics involved. At the same time, further research and development of haptic materials is required by manufacturers.

Biocompatible Materials↗
PubMed1991

[Marked bone marrow necrosis preceding acute myeloblastic leukemia in childhood].

A 3-year-old boy was transferred to our hospital because of fever, abdominal pain and severe systemic bone pain on October 16, 1989. Hematological examination showed hemoglobin 8.7 g/dl, white blood cell count 5300/microliters with 9% neutrophils and platelet count 5.5 x 10(4)/microliters. Bone marrow aspiration and biopsy revealed markedly necrotic cells. Blood chemistry showed transient elevation of CRP, serum LDH, FDP, FDP-Ddimer and fibrinogen. Tc99m pyrophosphate bone scanning showed multiple uptake spots in various bone. Although the sign of fever, abdominal pain and bone pain disappeared spontaneously after three weeks, anemia persisted. About two months later from bone marrow necrosis, abnormal cells appeared in the bone marrow. A diagnosis of AML (M3) was made and a combination chemotherapy started. This case is remarkable for elevation of acute phase protein in association with bone marrow necrosis.

Bone Marrow↗