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Biomedical subjects

J Suzuki

Publications and source records attributed to J Suzuki.

At least 307 records · Page 17Linked to original sources

Enhancement of the binding of triglyceride-rich lipoproteins to the very low density lipoprotein receptor by apolipoprotein E and lipoprotein lipase.

The low-density lipoprotein (LDL) receptor plays a crucial role in cholesterol metabolism. A related protein, designated the very low density lipoprotein (VLDL) receptor, that specifically binds apolipoprotein (apo) E has recently been characterized and shown to be expressed in heart, muscle and adipose tissue and the human monocyte-macrophage cell line THP-1. The VLDL receptor binds and internalizes VLDL and intermediate density lipoprotein from Watanabe heritable hyperlipidemic (WHHL) rabbits as well as beta-migrating VLDL from cholesterol-fed rabbits but not LDL from WHHL rabbits. Chinese hamster ovary (CHO) cells transfected with the rabbit VLDL receptor cDNA have now been shown to bind or internalize VLDL (d < 1.006 g/ml) isolated from fasted normolipidemic human subjects with lower affinity than WHHL-VLDL or rabbit beta-VLDL. However, binding and internalization were markedly enhanced when fasted human VLDL was preincubated with either recombinant human apoE (3/3) or lipoprotein lipase (LPL) in CHO cells overexpressing the rabbit or human VLDL receptor. CHO cells transfected with both the rabbit VLDL receptor cDNA and the human LPL cDNA effectively bound, internalized, and degraded fasted human VLDL without pretreatment. Treatment of heparinase reduced the effect of LPL-mediated binding at 4 degrees C, but the inhibitory effect was lower at 37 degrees C. Pseudomonas LPL also enhanced the binding of human fasted VLDL to the VLDL receptor at 37 degrees C in CHO cells overexpressing the human VLDL receptor. Taken together, LPL causes the enhancement of triglyceride-rich lipoproteins binding to the VLDL receptor via both the formation of bridge between lipoproteins and heparan sulfate proteoglycans and its lipolytic effect. Ligand blot analysis showed that the apparent molecular mass of the VLDL receptor is 118 kDa, which is smaller than that of the LDL receptor. These results indicate that the VLDL receptor recognizes both triglyceride-rich lipoproteins that are also relatively rich in apoE, as well as the remnants of triglyceride-rich lipoproteins after catabolism and the interaction with heparan sulfate proteoglycans by LPL. The VLDL receptor may thus function as a receptor for remnants of triglyceride-rich lipoproteins in extrahepatic tissues.

Apolipoproteins E↗

Antithrombotic activity of a symmetrical triglyceride with eicosapentaenoic acid and gamma-linolenic acid in guinea pig mesenteric microvasculature.

The antithrombotic effect of a synthetic symmetrical triglyceride having eicosapentaenoic acid (EPA) at positions 1 and 3, and gamma-linolenic acid (GLA) at position 2 was investigated. Administration of the triglyceride significantly increased thrombus formation time and thrombotic occlusion time induced by light irradiation and a fluorescent dye in guinea pigs after 14 days administration compared to that of soybean oil. The antithrombotic effect of the triglyceride was similar to that of EPA ethyl ester. Administration of the triglyceride increased GLA, dihomo-gamma-linolenic acid (DGLA) and EPA contents in plasma and the liver, and the ratio of DGLA to arachidonic acid. These results might be responsible for this antithrombotic effect.

8,11,14-Eicosatrienoic Acid↗

Lipid accumulation and foam cell formation in Chinese hamster ovary cells overexpressing very low density lipoprotein receptor.

The rabbit very low density lipoprotein receptor gene was introduced into LDL receptor-negative Chinese hamster ovary cells (ldl-A7). Incubation of the transfected cells with rabbit beta-VLDL (5 to 8 micrograms protein/ml), for 6 days, induced foam cell formation. The cells accumulated lipid droplets visualized by oil red-O staining; the cellular cholesteryl ester and triglyceride content increased two- to threefold. [3H]Oleate incorporation into cholesteryl [3H]oleate was stimulated threefold by incubation of cells with beta-VLDL (20 micrograms protein/ml). Northern blot analysis revealed the presence of VLDL receptor mRNA in rabbit resident alveolar macrophages. Incubation of the macrophages with beta-VLDL (20 micrograms protein/ml) for 24 hours induced foam cell formation but had virtually no effect on VLDL receptor mRNA abundance. These results suggest that the VLDL receptor on macrophages may play an important role in foam cell formation.

Animals↗

Ontogeny of neuropsin mRNA expression in the mouse brain.

In our previous study, we found a novel gene encoding a serine protease termed neuropsin (NP) which exhibited activity-dependent gene expression or repression in the mouse hippocampus (Chen et al., 1995). In the present study, we examined the ontogeny of NP mRNA expression by in situ hybridization in the brain. Weak hybridization signals were also observed in the choroid plexus at this stage in addition to neuronal labeling. The signals continued to show this localization pattern until postnatal day 12. After embryonic day 18, the number of hybridization signals localized in the neurons of the forebrain limbic area were more predominant than those in the lower brainstem. NP gene expression spread in the anterior olfactory nucleus, hippocampus, septal nuclei, diagonal band of Broca, amygdala and limbic cortex successively from early embryonic to adult stage, though signals in the other brain regions were gradually decreased after birth. Thus, the widespread localization and two types of expression pattern, constitutive or transient, suggest that NP is a multiple functional protein involved in development, neuronal plasticity and cerebrospinal fluid production.

Animals↗

Changes in the urinary excretion level of 8-hydroxyguanine by exposure to reactive oxygen-generating substances.

A simple means of measuring of 8-hydroxyguanine (8-OHGua) levels in urine was developed. Rat and human urine samples were purified by means of strong cation exchange chromatography (Amberlite CG-120), followed by cellulose partition chromatography (Whatman CF-11). Thereafter, 8-OHGua was determined by means of high performance liquid chromatography (HPLC) using an electro-chemical detector. The level of 8-OHGua in rat urine increased by a factor of 2 to 4 after an intraperitoneal administration of 2-nitropropane (25 mg/kg), paraquat (11.3 mg/kg), or hydroquinone (11 mg/kg). On the other hand, the urine of smokers and persons exposed to air polluted with car exhaust also contained 1.9 and 3.8 fold more 8-OHGua, respectively, than that of control nonsmokers. These results indicated that the amount of 8-OHGua in urine is useful marker for monitoring the level of in vivo oxidative stress.

Adult↗

Transient disappearance of complete right bundle branch block during exercise in a patient with old inferior wall myocardial infarction.

To date, there has been no report of temporary disappearance of right bundle branch block (RBBB) during exercise. A patient with old infero-posterior myocardial infarction is described in whom complete RBBB disappeared transiently during treadmill exercise testing. No chest pain or significant ST-T changes occurred during and after the exercise periods. Any of the following mechanisms could have been involved: (1) the patient's complete RBBB might have been bradycardia-dependent, (2) an exercise-induced increase of sympathetic tone might have produced a temporary improvement of the conduction disturbances, or (3) the exercise might have elicited conduction disturbances in the main left bundle branch, which could have concealed a conduction delay in the main trunk of the right bundle branch.

Bundle-Branch Block↗

Cloning, sequencing, and expression in Escherichia coli of cDNA encoding porcine brain UMP-CMP kinase.

A cDNA encoding porcine brain UMP-CMP kinase has been isolated using two oligonucleotide probes synthesized on the basis of the partial amino acid sequences of the purified enzyme. The isolated cDNA consisted of 1,626 nucleotides including the coding region for a polypeptide of 196 amino acid residues with a calculated molecular weight of 22,279. The enzyme showed an overall sequence identity of about 40 and 50%, respectively, with adenylate kinases from mammalian muscle and Escherichia coli and UMP-CMP kinases from Saccharomyces cerevisiae and Dictyostelium discoideum. The two highly conserved residues, Thr-39 and Leu-66, in adenylate kinases, which are located close to the adenine ring of the bound AMP, are replaced by Ala and Ile, respectively, at the corresponding positions in UMP-CMP kinases. The entire structural gene was inserted 3'-downstream of the strong promoter in the expression plasmid pET-3b. E. coli BL21(DE3) cells carrying the resultant plasmid produced the active enzyme in a soluble state, most efficiently upon induction at 37 degrees C with 0.02 mM isopropyl-beta-D-thiogalactoside. The purified recombinant enzyme catalyzed specific phosphoryl transfer from ATP to UMP and CMP.

Adenylate Kinase↗

[Properties of a hemolysin produced by group C streptococci isolated from hemolytic streptococcal infection in formosan squirrels].

The hemolysin produced by group C streptococci (GCH) has an isoelectric point (pI) of 5.6 and a molecular weight of 32,000 and shows hemolytic activity in the absence of 2-mercaptoethanol (2-ME). The hemolytic activity of GCH was compared to that of streptolysin S (SLS). These hemolysins did not differ with respect to the binding and release of hemoglobin (Hb). GCH was bound to phospholipids on the membranes of target erythrocytes, followed by the rapid released of K+ and slow Hb release after a relatively long lag time. GCH showed a lower hemolytic efficiency than SLS, reflecting the fact that these hemolysins destroy erythrocytes by slightly different mechanisms.

Animals↗

[Clinico-pathological aspect of HIV-sero positive inpatients].

To describe the clinico-pathological aspect of HIV/AIDS inpatients, we reviewed HIV/AIDS inpatients in our hospital since 1988. We evaluated risk factors, CD4 counts, CD4/8 ratio, cause of death and the survival time after diagnosis of AIDS. A total of 13 HIV sero-positive subjects were admitted to our hospital, including 11 cases (85%) with AIDS. One patient was a foreigner. All cases were male; age range 18-70 years. Hemophiliacs and sexually transmitted patients account for 62% and 38% of cases, respectively. There were no cases of intravenous drug users. In all cases with AIDS, CD4+ cells and CD4/8 ratio significantly decreased with median value of 73/microns and 0.18, respectively. Six cases (54%) were decreased and autopsy were done in four cases. Findings of autopsy revealed HIV encephalopathy and systemic various infection, including Pneumocystis carinii, cytomegalovirus, papilloma virus and pox virus. Cytomegalovirus infection was found in all cases; one had innumerable inclusion bodies in lung, adrenal gland and intestines. The median survival time after diagnosis of AIDS were 26 months.

AIDS-Related Opportunistic Infections↗

Semicircular canal contributions to the three-dimensional vestibuloocular reflex: a model-based approach.

1. We studied the contribution of the individual semicircular canals to the generation of horizontal and torsional eye movements in cynomolgus monkeys. Eye movements were elicited by sinusoidal rotation about a vertical (gravitational) axis at 0.2 Hz with the animals tilted in various attitudes of static forward or backward pitch. The gains of the horizontal and torsional components of the vestibuloocular reflex (VOR) were measured for each tilt position. The gains as a function of tilt position were fit with sinusoidal functions, and spatial gains and phases were determined. After control responses were recorded, the semicircular canals were plugged, animals were allowed to adapt, and the test procedure was repeated. Animals were prepared with only the anterior and posterior canals intact [vertical canal (VC) animals], with only the lateral canals intact [lateral canal (LC) animal], and with only one anterior and the contralateral posterior canals intact [right anterior and left posterior canal (RALP) animals; left anterior and right posterior canal (LARP) animals]. 2. In normal animals, the gain of the horizontal (yaw axis) velocity of the compensatory eye movements decreased as they were pitched forward or backward, and a torsional velocity appeared, reversing phase at the peak of the horizontal gain. After the anterior and posterior canals were plugged (LC animal), the horizontal component was reduced when the animal was tilted backward; the gain was zero with about -60 degrees of backward tilt. The spatial phase of the torsional component had the same characteristics. This is consistent with the fact that both responses were produced by the lateral canals, which from our results are tilted between 28 and 39 degrees above the horizontal stereotaxic plane. 3. After both lateral canals were plugged (VC animals), horizontal velocity was reduced in the upright position but increased as the animals were pitched backward relative to the axis of rotation. Torsional velocities, which were zero in the upright position in the normal animal, were now 180 degrees out of phase with the horizontal velocity. The peak values of the horizontal and torsional components were significantly shifted from the normal data and were closely aligned with each other, reaching peak values at approximately -56 degrees pitched back (-53 degrees horizontal, -58 degrees torsional). The same was true for the LARP and RALP animals; the peak values were at -59 degrees pitched back (-55 degrees horizontal, -62 degrees torsional). Likewise, in the LC animal the peak yaw and roll gains occurred at about the same angle of forward tilt, 35 degrees (30 degrees horizontal, 39 degrees torsional). Thus, in each case, the canal plugging had transformed the VOR from a compensatory to a direction-fixed response with regard to the head. Therefore there was no adaptation of the response planes of the individual canals after plugging. 4. The data were compared with eye velocity predictions of a model based on the geometric organization of the canals and their relation to a head coordinate frame. The model used the normal to the canal planes to form a nonorthogonal coordinate basis for representing eye velocity. An analysis of variance was used to define the goodness of fit of model predictions to the data. Model predictions and experimental data agreed closely for both normal animals and for the animals with canal lesions. Moreover, if horizontal and roll components from the LC and VC animals were combined, the summation overlay the response of the normal monkeys and the predictions of the model. In addition, a combination of the RALP and LARP animals predicted the response of the lateral-canal-plugged (VC) animals. 5. When operated animals were tested in light, the gains, peak values, and spatial phases of horizontal and roll eye velocity returned to the preoperative values, regardless of the type of surgery performed. This indicates that vision compensated for the lack o

Animals↗

Bopindolol is a slowly dissociating beta 1-adrenoceptor antagonist when compared to other beta-blockers.

This study used radioligand binding assay methods and pharmacological experiments to examine whether bopindolol, possessing a long-lasting action in addition to potent beta-adrenoceptor antagonistic effects, is a slowly dissociating antagonist. In addition, the slow dissociation of two of its metabolites, 18-502 (4-(3-tert-butylamino-2-hydroxypropoxy)-2-methyl indole) and 20-785 (4-(3-tert-butylaminopropoxy)-2-carboxyl indole), which have potent beta-blocking activities, was also assessed. The blockade of 3H-CGP12177 binding sites in rat heart and brain induced by pindolol was readily reversed by washing, whereas this inhibition by bopindolol and 18-502 was not easily reversed by washing. In addition, specific bindings of the hearts of the treatment animals with 20-785, atenolol, (+/-)propranolol, nadolol and celiprolol and of washout were 86.7, 78.8, 77.5, 82.3 and 79.9% of the control, respectively. These blockades by the treatment of each drug and washout in the brain were, however, lower than those in the hearts. On the other hand, when the left and right atria were pretreated with propranolol, bopindolol and 18-502, the inotropic and chronotropic actions of isoprenaline were inhibited by these drugs even though they were not present in the extracellular medium. Pretreatment with 20-785, atenolol and nadolol was readily reversed for both inotropic action and chronotropic rate, and inhibition by celiprolol and pindolol remained at 25% of the control at 240 min after treatment with these drugs. A good correlation between inhibitory binding percentage in the hearts and inhibitory inotropic or chronotropic actions were observed, although it was not observed in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-1 Receptor Antagonists↗

A questionnaire survey on the use of dust respirators among lead workers in small scale companies.

In order to find out whether dust respirators are properly used among lead workers in small scale manufacturing companies of lead pigments and stabilizers, a questionnaire survey was carried out for 141 lead workers. The questionnaire consisting of 7 items of questions including selection, use, maintenance, storage and instruction of respirators was distributed to all 141 workers. This survey revealed that 22% of the total workers wore unauthorized dust respirators, and that 73% used a knitcover. Instruction by health supervisors of how to use and where to store the respirators was found to be effective for inspection of valve and a proper place to store dust respirator. However, the result that significantly large percentage of workers used the knitcover following the health supervisors' instruction can be taken to indicate that health supervisors should be given more precise information on deteriorated face-sealing of the respirator facepiece with the knitcover.

Chi-Square Distribution↗

Temporal bone findings in Cogan's syndrome.

We report on the pathological findings in temporal bones taken from a 92-year-old man who had been diagnosed as suffering from Cogan's syndrome before death. Extensive endolymphatic hydrops was observed in the cochlea of the right ear. The saccule showed a collapse following intense dilation. Outpouching of the utricle and crus commune was found and the perilymphatic space of the posterior semicircular canal was occupied by the fibrotic tissue. The left ear showed neither hydrops nor fibrosis. There was absorption of the enchondral bone in both ears, but in the blood vessels there were no pathological changes.

Aged↗

Afternystagmus, its specific features.

There are important issues and new observations concerning 'afternystagmus'. Recent findings were mostly supplied by 3-dimensional records of eye movements. 'After-nystagmus' appears to be secondary to the reactions to the visual and vestibular inputs. The beginning of afternystagmus, however, is not always clear, and the distinction from the primary reaction is not clear either. The axis of eyeball rotation during afternystagmus is not necessarily the same as that of the primary reaction, but frequently changes gradually with time. The change in the plane of eyeball rotation during afternystagmus appears to follow a certain rule, which appears to be under specific influences from the otolith organs. Afternystagmus and its related phenomena seem to be explained by a hypothetical 'velocity storage'.

Adult↗

Effects of semicircular canal plugging on caloric nystagmus recorded in three dimensions.

In Rhesus monkeys, distinct eye movement response components in the planes of the semicircular canals (canal plane vectors, CPV) were identified by 3-dimensional recordings of caloric nystagmus elicited in different head positions relative to gravity. Surgical plugging of single semicircular canals (SCC) was used to identify the generators of these response components. The lateral CPV is a sinusoidal function of head position, compatible with a thermovective mechanisms in this canal. Surgical plugging of the lateral SCC leaves only a small head position independent, lateral CPV, probably due to direct temperature effects on lateral SCC afferents. The posterior and anterior CPVs are complex responses composed of various components of which the present plugging experiments identified two generators: i) effects of thermovection in the lateral SCC, demonstrated by modifications of posterior and anterior CPVs after occlusion of the lateral SCC; and ii) thermovection in the vertical SCCs, demonstrated by effects of plugging a single vertical SCC exclusively on the corresponding CPV. This is the first definite identification of the vertical SCCs as contributors to the generation of nystagmus induced by caloric irrigation of the outer ear canal. It may provide a basis for the development of a modified caloric test measuring more than only lateral canal function in human patients.

Animals↗