Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 613 records · Page 34Linked to original sources

PubMed1990

Investigations on the presence of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase, E.C.1.1.1.34) in lenses of various animal species.

The cholesterol requirements of the lens for the formation of plasma membranes are met by self-synthesis immediately after birth, this capacity, however, decreases considerably with increasing age, so that the deficit can only be met by exogenous supply. These findings are of great importance with respect to the qualitative assessment of extra-hepatical side effects of the substance class of HMG-CoA-reductase inhibitors on possible disturbances of lens transparency. In contrast to investigations of Mosley et al. (23) with rat and rabbit lenses, we did not find any activity of the HMG-CoA-reductase in our experiments with the lens cortex of calf, bovine, Beagle dog. The disturbances in lens transparency observed in chronical toxicity tests with high doses of HMG-CoA- reductase inhibitors might rather be due to the impairment of the exogenous cholesterol supply by a considerable decrease of the normal cholesterol level in the blood. The therapeutical treatment of pathologically increased blood cholesterol levels of patients should therefore not affect the transparency of human lenses. Relevant drug-safety-clinical studies confirm this experimentally substantiated supposition.

Animals↗

PubMed1990

[Ischemic heart disease evaluated using dipyridamole-stress two-dimensional echocardiography].

Dipyridamole-stress two-dimensional echocardiography (2DE) was performed in 25 subjects, 14 with stenotic and 11 with normal coronary arteries by coronary angiography, to assess the sites and severity of coronary artery stenosis noninvasively. Dipyridamole was administered intravenously with a dose of 0.56 mg/kg for 4 min. 2DE was recorded at the lower papillary muscle level and the percent fractional area change (% FAC) of the left ventricular segments was computed (FV). In all cases with an echocardiographic regional wall motion abnormality in the interventricular septum, a significant stenosis (greater than or equal to 75%) was documented angiographically in the left anterior descending coronary artery (LAD). In seven of eight patients with a segmental abnormality in the inferolateral wall, a significant stenosis was observed in the left circumflex coronary artery (Cx). The sensitivity and specificity of dipyridamole-stress echocardiography were 100% and 92%, respectively, for an LAD stenosis, and and 87.5% and 71%, respectively, for a Cx stenosis. The segmental wall motion abnormality induced by dipyridamole resolved within four to five min after terminating the infusion in patients with coronary artery narrowing of 75%; whereas, it persisted up to six to seven min in patients with 90% narrowing. There was no improvement in the LV wall motion 15 min after the termination of the infusion in patients with severe narrowing (99%). In conclusion, dipyridamole-stress echocardiography proved to be one of the most useful methods, not only for detecting coronary artery disease, but for predicting the severity and for localizing the sites of lesions as well.

Analysis of Variance↗

PubMed1990

[Durability of bonding between 4-META/MMA-TBB resin to dentin pretreated with 10-3. The effect of 10-3 pretreating period and subsequent glutaraldehyde treatment].

Adhesion durability between dentin pretreated with 10-3 and 4-META/MMA-TBB resin was studied. Reduction of etching periods with 10-3 was not so effective as expected. The weakening of bond strength during immersion in water at 37 degrees C to the dentin pretreated for 1 sec occurred faster than those for either 5 sec or 10 sec. The strength decreased from 12 MPa at 1 day to 9 MPa at 3 months, 3 MPa at 6 months and finally 2 MPa at 1 year in the case of 1 sec pretreated dentin. On the other hand, the strength became half after the storage in water for 1 year in the cases of 5 and 10 sec pretreated dentins. Combination of 10-3 pretreatment and subsequent glutaraldehyde treatment could stabilize the decrease but not completely. SEM and TEM examinations suggested that dentinal collagen exposed by the etching but not entangled and impregnated by poly (4-META-co-MMA) easily deteriorated by water during the longer immersion. Collagen modified with 10-3 and then with glutaraldehyde was also changed by the longer immersion.

Acid Etching, Dental↗

PubMed1990

Alteration in sarcoplasmic reticulum-dependent contraction of tail arteries in response to caffeine and noradrenaline in spontaneously hypertensive rats.

Since the membrane Ca2+ handling properties of the arterial smooth muscle sarcoplasmic reticulum may be altered in genetic hypertension, we studied caffeine- and noradrenaline-induced contractions in tail arteries from spontaneously hypertensive rats (SHR) at the prehypertensive stage (4 weeks old) and from age-matched Wistar-Kyoto rats (WKY). After the sarcoplasmic reticulum had been loaded with Ca2+ by pretreatment with physiological Ca2+ solution, caffeine- and noradrenaline-induced contractions of the tail arteries, measured in a Ca2(+)-free solution [containing 0.1 mmol/l ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraace tic acid], were smaller in SHR than in WKY. After caffeine-releasable Ca2+ in the sarcoplasmic reticulum had been depleted by pretreatment with the Ca2(+)-free solution, the caffeine-induced arterial contractions in a low-Ca2+ (0.5 mmol/l) solution were smaller in SHR than in WKY. The Ca2+ concentration-tension relationship in skinned arterial fibres was similar in WKY and SHR. These data suggest that the ability of the sarcoplasmic reticulum to take up and store caffeine- and noradrenaline-releasable Ca2+ is decreased in SHR. The development of hypertension in SHR may be explained by an impaired function of the sarcoplasmic reticulum in arterial smooth muscle.

Animals↗

PubMed1990

Estimation of permeability in blood-retinal barrier.

Permeability of the blood-retinal barrier (BRB) can be determined by vitreous fluorophotometry and computer analysis. In this study, we characterize our eye model and apply it to normal human subjects. In this investigation of BRB permeability, we employed four parameters for the eye model: the inward permeability (Pin) and outward permeability (Pout) of the BRB; the diffusion coefficient in the posterior vitreous gel (D-p); and the plasma fluorescein concentration. The values of Pin, D-p, and plasma fluorescein concentration significantly affected the fluorescein concentration in the posterior vitreous 60 minutes after intravenous fluorescein injection. The value of Pout had little influence on the fluorescein kinetics in the posterior vitreous 60 minutes after injection. The results of experiments on humans indicate that the estimated values obtained by simulation fit satisfactorily the measured values. It is suggested that our computer simulation method in conjunction with vitreous fluorophotometry can effectively estimate permeability of BRB in normal and pathological eyes.

Adolescent↗

PubMed1990

Structure of novel glyceroglycolipids in Adzuki bean (Vigna angularis) seeds.

In addition to monoglycosyl diacylglycerol, three glyceroglycolipids with two to four hexose units were isolated from Adzuki bean seeds. Their structures were determined using enzymatic hydrolysis, permethylation analysis, nuclear magnetic resonance spectroscopy, and reversed-phase high pressure liquid chromatography, as folows: Gal(beta 1----3')- for the monoglycosyl diacyglycerol, Gal(alpha 1----6)-Gal(beta 1----3')- and Gal(beta 1----6)-Gal(beta1----3')- for the diglycosyl diacylglycerol, [Gal(beta 1----6]2-Gal(beta 1----3')- and Gal(beta 1----6)-Gal(alpha 1----6)-Gal(beta 1----3')- for the triglycosyl diacylglycerol, and [Gal(beta 1----6)]3-Gal(beta 1----3')- and [Gal(beta 1----6)]2-Gal(alpha 1----6)-Gal(beta 1----3')- for the tetraglycosyl diacylglycerol. Except for Gal(alpha 1----6)-Gal(beta 1----3')-diacylglycerol, all of the glycolipids with oligosaccharide moieties had novel glycosidic linkage patterns differing from those in the well-known glyceroglycolipids in nature. The predominant diacylglycerol species component was characterized as dilinolenin. However, the molecular species composition of the diacylglycerol moieties of the two diglycosyl isomers with different glycosidic linkage patterns were found to be qualitatively the same but different quantitatively, as follows: in the well-known isomer Gal(alpha 1----6)-Gal(beta 1----3')-, 39% dilinolenin, 15% palmitoyl linolenin, and 14% linoleoyl linolenin; and in the novel isomer Gal(beta 1----6)-Gal(beta 1----3')-, 35% dilinolenin, 24% dilinolein, and 21% linoleoyl linolenin.

Carbohydrate Sequence↗

PubMed1989

B-cell lymphoma associated with eosinophilia.

A case of non-Hodgkin's lymphoma associated with eosinophilia is reported. The lymphoma was of the diffuse, large-cell type and was of B-cell origin. The number of eosinophils decreased with combination chemotherapy, along with a reduction in the size of the lymph nodes. Eosinophilia reappeared with the regrowth of lymphoma. The relationship between B-cell lymphoma and eosinophilia is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Cloning and sequence analysis of cDNA encoding a precursor for rat brain natriuretic peptide.

Brain natriuretic peptide (BNP) is a new type of natriuretic peptide, which has so far been identified only in porcine brain and atrium. Immunological observations suggest that rat and porcine BNP may have structural difference according to species. To identify rat BNP, we constructed a rat atrial cDNA library, and screened for clones encoding rat BNP-precursor by using part of porcine BNP cDNA as a probe. By sequencing a cloned cDNA, the amino acid sequence of rat BNP-precursor comprising 121 residues was deduced as carrying a 26-residue putative signal peptide at the N-terminus and a region homologous to porcine BNP-32 at the C-terminus. In addition, remarkably high homology between rat and porcine BNP-precursors was observed in the 3'-untranslated AT-rich region. Comparing sequences of precursors of ANP and BNP thus far identified, structural and processing features characteristic of the BNP family were discussed.

Amino Acid Sequence↗

PubMed1989

Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide.

Brain natriuretic peptide (BNP) is a novel diuretic-natriuretic and vasorelaxant peptide originally isolated from porcine brain. In contrast to mammalian atrial natriuretic peptide (ANP), immunological characterization suggests that mammalian BNPs show structural species differences. In order to determine the amino acid sequence of human BNP, we constructed a human cardiac atrium cDNA library and screened for clones hybridizing with porcine BNP cDNA. By sequence analysis of cDNA encoding a putative human BNP precursor, an amino acid sequence of human prepro-BNP of 134 residues has been deduced, in which a minimum bioactive unit highly homologous to porcine BNP-32 is present at the carboxy-terminus.

Amino Acid Sequence↗

PubMed1989

Sodium channel-blocking properties of flecainide, a class IC antiarrhythmic drug, in guinea-pig papillary muscles. An open channel blocker or an inactivated channel blocker.

Effects of flecainide (a class IC antiarrhythmic drug) on the maximum rate of rise (Vmax) of action potentials (APs) were studied in guinea-pig papillary muscles, with special reference to their time, voltage, and action potential duration (APD) dependence in the presence and absence of nicorandil. Nicorandil was used to shorten APD, i.e., the time period of inactivation state of sodium channels. APs were recorded from the preparations using standard microelectrode techniques. Flecainide (5 mumol/l) reduced Vmax without changing resting potential, AP amplitude, APD50, and APD90 examined at 1 Hz. The drug shifted the normalized Vmax-membrane potential curve (examined at 1/60 Hz) in the hyperpolarizing direction by 3.1 +/- 0.8 mV (n = 6) (voltage dependence). The drug caused a frequency-dependent reduction of Vmax at greater than or equal to 0.1 Hz, developed a use-dependent reduction of Vmax at 1 Hz with an onset time constant of 11.7 +/- 0.4 s (n = 6), and slowed the recovery process of Vmax, whose resultant recovery time constant was 19.9 +/- 1.2 s (n = 6) (time dependence). These flecainide-induced time-dependent reductions of Vmax were not antagonized by nicorandil (1 mmol/l) which shortened APD to about 1/4 of control (APD independence). These results suggest that flecainide is primarily an open channel blocker because its channel-blocking actions are independent of APD or the time period of inactivation.

Action Potentials↗

PubMed1989

Spread of herpes simplex virus type-1 (Miyama +GC strain) to the central nervous system after intraperitoneal inoculation: the role of the myenteric plexus of the gut.

The pathways taken by the HSV-1 virus after intraperitoneal (i.p.) inoculation were studied in 5-week old male C3H/HeN mice injected with 1 x 10(4) PFU (100 LD50) or 5 x 10(5) PFU (5000 LD50) of HSV-1 (Miyama +GC strain). At the higher dosage (5 x 10(5) PFU), HSV-1 began replicating in the adrenal from the first day, then in the gut and thoracic portion of the spinal cord by the third day, and in the brainstem by the fourth day, as shown by the titers of the virus in these organs. By immunoperoxidase staining HSV-1 was localized in a necrotic area of the adrenal, the myenteric plexus of the gut, the intermediolateral columns of the thoracic cord, and the vagus nerve nuclei of the medulla oblongata. In the low dose mice (1 x 10(4) PFU), HSV-1 was not isolated from the adrenal or thoracic segment of the spinal cord from the time of inoculation until the time of death. It was, however, isolated from the gut on days 4-6 and from the brainstem by day 5. HSV-1 was never isolated from the blood of either group at any time. The localizations of viral replication suggest that in the mice inoculated with 1 x 10(4) PFU, HSV-1 spreads to the brainstem via the vagal nerves after replication in the myenteric plexus of the gut. In the mice given the higher dose, localizations suggest not only the above route, but also that the virus spread to the intermediolateral columns of the spinal cord after replicating in the adrenal.

Animals↗

PubMed1989

Synthesis and evaluation of 11C-PK 11195 for in vivo study of peripheral-type benzodiazepine receptors using positron emission tomography.

The biodistribution of 3H-PK 11195, an antagonist of the peripheral-type benzodiazepine receptors, was studied in mice. High accumulations of radioactivity in the heart, lung, spleen, kidney and adrenal were observed after intravenous injection of tracer amounts of 3H-PK 11195 into the mice. The radioactivity in the heart, lung, spleen, kidney and adrenal was significantly decreased by the coadministration of carrier PK 11195, which indicated that PK 11195 specifically binds to the receptors. No radioactive metabolites were observed in the heart, lung and brain 20 min after intravenous administration of 3H-PK 11195. The accumulation of 3H-PK 11195 in the lung was not affected by pretreatment with either alpha-methyl benzylamine or imipramine, suggesting that 3H-PK 11195 specifically binds to the receptors. The ratios of radioactivity of the kidney, adrenal and spleen to blood increased as a function of time, whereas that of the lung and heart rapidly reached to a steady state. 11C-PK 11195 was synthesized by the N-methylation of desmethyl precursor yielding more than 100 mCi with high specific activity (more than 1.4 Ci/mumol). The labeling and purification procedure was completed within 23 min after the end of bombardment (EOB). The 11C-PK 11195 solution for injection seems to have a high potential for the in vivo study of the peripheral-type benzodiazepine receptors in the living human by means of positron emission tomography (PET).

Animals↗

PubMed1989

Effect of long-term treatment with beta-blocker on cardiac hypertrophy in SHR.

Recent studies suggest that beta-blocker treatment may attenuate cardiac hypertrophy induced by pressure overload in the spontaneously hypertensive rat (SHR), but the effect of this therapy on the reconstitution of the intracellular constituents in the heart that occurs during the development of cardiac hypertrophy has not been examined. In this study, we investigated the effect of chronic administration of carteolol (4 mg/kg/day p.o.) or propranolol (20 mg/kg/day p.o.), beta-blockers with distinct modes of action, on the composition of cardiac myosin isozymes and histological findings as well as heart weight. Therapeutic periods were 4, 12 or 30 weeks. Though blood pressure was not significantly reduced, the development of cardiac hypertrophy was suppressed as evidenced by left ventricular weight in both groups of carteolol- and propranolol-treated SHR for all therapeutic periods. Again, beta-blocker treatment for 12 weeks alleviated myocardial degeneration and reactive fibrosis which were observed in all cases of age-matched untreated SHR. However the extent of the transition of cardiac myosin isozymes from V1 to V2 or V3 were essentially the same among all groups including untreated SHR. These results indicate that chronic administration of beta-blockers attenuates the development of cardiac hypertrophy and degeneration without affecting the transition of myosin isozymes which is thought to be a kind of biochemical adaptation of the myocardium to overload.

Adrenergic beta-Antagonists↗

PubMed1989

Biomembranes as models for polymer surfaces. V. Thrombelastographic studies of polymeric lipids and polyesters.

Our approach to the design of haemocompatible biomaterials is based upon the concept that coating a polymer or metal surface with phosphatidylcholine polar groups (corresponding to the major phospholipid of the human erythrocyte outer cell membrane) will improve their haemocompatibility. We have examined the effect on blood coagulation of a number of substrates: those normally used in prosthetic devices such as polyethylene terephthalate (Dacron), expanded polytetrafluoroethylene, silicone and new polymers which contain the phosphatidylcholine head group (phosphorylcholine). The effect on coagulation of blood exposed to these substrates was determined by the technique of material thrombelastography, a relatively new method for the in vitro screening of biomaterial thrombogenicity. The results obtained with Dacron, polytetrafluoroethylene and silicone are compared with those obtained with a phospholipid-dipalmitoyl-phosphatidylcholine, a polymerized phospholipid-diacetylenicphosphatidylcholine, and a range of recently synthesized polyesters, each of which contains the phosphorylcholine polar head group.

Biocompatible Materials↗

PubMed1989

Micronucleus test with cyclophosphamide administered by intraperitoneal injection and oral gavage.

The effect of route of administration on the micronucleus test was examined in 2 laboratories: cyclophosphamide (CYP) was administered by intraperitoneal injection (i.p.) or oral gavage (p.o.) to 2 strains of mice. MS/Ae and CD-1. On the basis of a small-scale acute toxicity study and a pilot micronucleus experiment, the final micronucleus test was performed with a 48-h sampling time at doses of 25-200 mg/kg i.p. and 50-400 mg/kg p.o. CYP via the i.p. route was more toxic and induced more micronucleated polychromatic erythrocytes (MNPCEs) in MS/Ae mice than in CD-1 mice. Administration-route-related differences were not distinctly shown in the MS/Ae strain. In CD-1, however, higher doses were required for the p.o. route than for the i.p. route to induce about equal amounts of clastogenic damage.

Administration, Oral↗

PubMed1989

Cytokines produced in lymph follicles.

The events occurring inside lymph follicles during a germinal center reaction are poorly understood. Using B and T lymphoid cell populations prepared from human tonsillar lymph follicles, and enriched or not in macrophages or in follicular dendritic cells, we examined the production of cytokines by these cells in vitro. Interleukin 6 (IL-6) and tumor necrosis factor (TNF) were found in the supernatants of cultures stimulated with phytohemagglutinin or pokeweed mitogen. IL-1 beta was occasionally detected; its secretion apparently depends on the origin of the tonsils, the stimulation, and the cell populations. IFN-gamma and IL-2 were not produced in significant amounts by these lymph follicle cells. IL-4 was only found in very low concentrations in the supernatant of the different cell cultures. The cell populations containing follicular dendritic cells produced more IL-6 and TNF than the others, especially than those composed of only B and T cells.

Adenoids↗

PubMed1989

Potential tumor- or organ-imaging agents. 29. Radioiodinated esters and amides of 20-hydroxy- and 20-aminopregn-5-en-3 beta-ols.

Radioiodinated benzoyl esters and amides of epimeric 20-hydroxy- and 20-aminopregn-5-en-3 beta-ols were synthesized in an effort to find an agent that would be rapidly and selectively taken up by adrenal cortical tissue. Achievement of such a goal would provide a basis for the development of adrenal imaging agents superior to those currently available for clinical use. The iodobenzoyl derivatives were obtained by treating the appropriate epimer with 2-iodobenzoic acid in the presence of dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine. The resulting esters and amides were readily labeled with radioiodine by isotope exchange with sodium iodide-125 in pivalic acid. Tissue distribution studies in female rats revealed that only the esters displayed appreciable adrenal specificity, and the ester having the same configuration at C-20 as cholesterol was significantly better than the corresponding C-20 epimer.

Adrenal Cortex↗

PubMed1989

Preparation and characterization of antibodies against 3,2'-dimethyl-4-aminobiphenyl-modified DNA.

Polyclonal antibodies for 3,2'-dimethyl-4-aminobiphenyl (DMAB)-DNA adducts were obtained from the sera of rabbits immunized with N-OH-DMAB-modified DNA. Using the enzyme linked immunosorbent assay (ELISA), these antibodies were shown to recognize DNA modified by N-OH-DMAB and N-hydroxy-4-aminobiphenyl, but not unmodified DNA, 2-acetylaminofluorene- or 4-nitroquinoline-1-oxide-modified DNA, free aminobiphenyl or DMAB derivatives. Using competitive ELISA with DMAB-modified denatured DNA, a 50% inhibition of antibody antigen binding was caused by 7 fmol of DMAB adducts applied to each assay well as an inhibitor. Native DNA bearing adducts was associated with 50% inhibition in the range of 22-90 fmol/asay well, depending on the levels of modification. The adducts recognized by the antibody were shown to be stable against treatment of heat or alkali denaturation. Optimal conditions for the detection of adducts in DNA from the rat organs exposed to DMAB were established by means of competitive ELISA, using alkaline-denatured DNA as an inhibitor. Thus, as little as 5 fmol adducts in 1 microgram of DNA could be detected. Indirect immunofluorescence staining indicated that anti-DMAB-DNA antibodies bound specifically to nuclear components of rat fibroblast 3Y1 cells treated with N-OH-DMAB. The intensity of the fluorescence was proportional to the dose of carcinogen administered. The antibodies should be helpful for use in studies on the formation of adducts and their removal in cells and tissues after DMAB administration.

Aminobiphenyl Compounds↗