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Biomedical subjects

Y Nishikawa

Publications and source records attributed to Y Nishikawa.

At least 163 records · Page 9Linked to original sources

Accelerated myocardial relaxation in conscious dogs during acute cardiac tamponade.

Eight chronically instrumented conscious dogs were used to test the hypothesis that left ventricular (LV) relaxation is accelerated during cardiac tamponade. The time constant of LV transmural pressure fall was measured before and during intrapericardial (IP) saline infusion (baseline) with and without beta-adrenergic blockade (propranolol 1 mg/kg iv). Heart rate was controlled by atrial pacing. Increasing IP pressure caused a progressive linear decrease in stroke volume before and during beta-blockade in each animal. The time constant of LV transmural pressure fall also decreased continuously with an increase in IP pressure from 26 +/- 7 ms during baseline to 18 +/- 5 ms during severe cardiac tamponade (P < 0.01) before beta-blockade. However, after beta-blockade, the time constant of LV transmural pressure fall was constant over a wide range of IP pressures despite a continuous decrease in LV end-diastolic volume. The time constant of LV transmural pressure fall was not altered by vena caval occlusions that caused the same decrease in LV preload observed during cardiac tamponade. We concluded that despite decreased pump function, LV relaxation was accelerated progressively during graded cardiac tamponade, and this change was dependent not on changes in loading conditions but on an intact beta-adrenergic influence.

Acute Disease↗

Cardiac myocyte function and left ventricular strains after brief ischemia and reperfusion in rabbits.

BACKGROUND: After a brief episode of ischemia, myocardial function may be depressed for prolonged periods despite reperfusion. The mechanisms of postischemic dysfunction differ depending on the experimental model. Regional ischemia and reperfusion in the intact animal provide a clinically relevant model, but experimental variables are difficult to control. Experimental conditions can be well controlled in isolated cardiac muscle and myocyte preparations, but these models are limited by the assumptions used to mimic ischemia and reperfusion. This study combines the unique advantages of both preparations. We characterized in vivo alterations in regional two-dimensional finite strains with ischemia and reperfusion produced in the intact animal, then isolated cardiac myocytes from the region with postischemic dysfunction to characterize in vitro function of postischemic myocytes. METHODS AND RESULTS: In seven anesthetized rabbits, three piezoelectric crystals were inserted in a triangular array to measure two-dimensional finite strains around the large coronary artery in the left ventricular anterior free wall. After 15 minutes of ischemia and reperfusion, strains were depressed at a stable level approximately 30% to 40% below control values between 1 and 6 hours after reperfusion. The direction of maximal shortening deformations was midway between circumferential and longitudinal directions during control and did not shift after reperfusion. In a second group of five rabbits, cardiac myocytes were isolated from the region with postischemic dysfunction after 15 minutes of ischemia and 45 minutes of reperfusion. We compared in vitro function in 45 postischemic myocytes with 48 cardiac myocytes isolated from five normal rabbits. Each rabbit (postischemic and control) contributed 9 +/- 1 (SD) myocytes to the study. All myocytes were studied within 1 hour after myocyte isolation (approximately 3 to 5 hours after reperfusion for postischemic myocytes). Myocytes were stimulated at 0.5 Hz and perfused with 2 mmol/L [Ca2+] Tyrode's solution to measure unloaded cell shortening. There was significantly less shortening in postischemic myocytes (12.4 +/- 2.1%) than control myocytes (16.2 +/- 1.2%). Maximal cell length (Lmax) was significantly longer in postischemic (134 +/- 7 microns) than control myocytes (122 +/- 7 microns), as was minimum cell length (Lmin) (118 +/- 8 versus 103 +/- 9 microns, respectively). The duration of shortening (time from stimulation to Lmin) was significantly shorter in postischemic (279 +/- 56 milliseconds) than control myocytes (405 +/- 44 milliseconds). Peak rates of cell shortening (-dL/dt) and lengthening (+dL/dt) did not differ. CONCLUSIONS: In rabbits, 15 minutes of ischemia produced a stable depression in finite strains for 1 to 6 hours after reperfusion, with shortening deformations reduced by approximately 30% to 40% without a shift in direction. Cardiac myocytes isolated from postischemic myocardium display functional impairments in vitro similar to those measured in vivo, with an approximately 25% reduction in unloaded myocyte shortening and decreased contraction duration. This indicates that ischemia and reperfusion induce intrinsic impairments in contractility independently of external loading conditions. This model may be useful for examining cellular mechanisms of postischemic myocardial dysfunction.

Animals↗

Identification of estrogen receptor in human adipose tissue and adipocytes.

Estrogen has various effects on adipose tissue. Although the presence of estrogen receptor (ER) has been demonstrated in rat adipose tissue and adipocytes, ER has not been identified in human adipose tissue. In this study, we demonstrated the existence of ER protein and ER messenger RNA (mRNA) in human sc adipose tissue and adipocytes. The cytosol fraction of human adipose tissue was partially purified by ammonium sulfate precipitation, and the presence of ER protein was analyzed by [3H]estradiol (E2) binding assay and Western blot analysis. [3H]E2 binding assay showed a low specific binding due to high nonspecific binding, and the dissociation constant (Kd) and maximal binding sites could not be obtained by Scatchard analysis. Western blots, however, showed the presence of ER protein in both the partially purified cytosol and nuclear fractions of human adipose tissue. The mol wt of ER in both fractions was approximately 66,000. Furthermore, Northern blot analysis of total RNA samples isolated from human adipose tissue showed the expression of ER mRNA at 6.2 kilobase in size. ER mRNA was also identified in isolated human adipocytes by the reverse transcription and polymerase chain reaction. These results indicated that both ER protein and ER mRNA are expressed in human adipocytes, suggesting that the effect of estrogen on human adipose tissues might involve a direct action.

Adipocytes↗

Administration of a branched-chain amino acid preparation during hepatic failure: a study emphasizing ammonia metabolism.

We administered a branched-chain amino acid (BCAA) infusion to 16 patients with hepatic failure and two healthy subjects, and then evaluated its effects on ammonia metabolism and amino acid metabolic pool. Immediately after the BCAA infusion, the venous blood ammonia concentration increased in 12 of 15 patients with hepatic failure and in both two healthy subjects. Glutamine (Gln) also rose in all cases following the BCAA infusion, and this rise was particularly marked in the hepatic failure group. The increase in Gln due to the BCAA infusion and the arteriovenous difference in the pre-administration ammonia concentration showed a good correlation. These results suggest an increase in glutamine cycle capacity in patients with hepatic failure.

Adult↗

[A case of Rubinstein-Taybi syndrome with bilateral vesicoureteral reflux].

The case was in a 7-month-old boy. Rubinstein-Taybi syndrome was diagnosed from the broad halluces and the characteristic physiognomy noticed since birth. He was brought to us at 7 months of age with fever as the chief complaint. Voiding cystourethrogram showed bilateral vesicoureteral reflux. The testis was palpable in the inguinal canal on either side, but could not be brought to the scrotum. No abnormalities were detected in the penis. From the above findings, he was diagnosed to have bilateral 4th degree vesicoureteral reflux and undescended testes as complicating Rubinstein-Taybi syndrome. The condition was treated by bilateral anti-reflux repair and bilateral orchidopexy at 8 months of age. There has been no recurrence of vesicoureteral reflux for 3 years. A brief discussion was made about the urological complications of Rubinstein-Taybi syndrome.

Cryptorchidism↗

Reversion of altered phenotype in primary cultured rat hepatocytes after intrahepatic and intrasplenic transplantation.

BACKGROUND: The phenotype of isolated rat hepatocytes changes during in vitro cultivation, but it is not clear whether this process turns back when the cells are returned to an in vivo milieu. Glutathione S-transferase placental form (GST-P), which is not expressed in hepatocytes in vivo, is induced within a few days of cultivation, whereas cytochrome P-450 constitutionally expressed in hepatocytes in vivo rapidly diminishes. We explored the dynamic nature of hepatocytic phenotypes using these two markers and intrahepatic and intrasplenic transplantation of cultured hepatocytes. EXPERIMENTAL DESIGN: Hepatocytes of F344 rats were isolated and cultured for 5 days to form spheroidal aggregates and then implanted into the livers and spleens of congenic analbuminemic rats. Expression of GST-P and P-450 was then examined immunocytochemically. In the intrahepatic case, the implanted hepatocytes could be distinguished from surrounding host hepatocytes by albumin immunostaining. RESULTS: The intrahepatically implanted hepatocytes turned GST-P-negative within 5 to 10 days, and re-expressed P-450 to a comparable level to that in surrounding host hepatocytes after 2 days. On the other hand, the hepatocytes implanted within spleens continued to express GST-P for 10 days, and started to express P-450 at extraordinarily high levels after 5 to 10 days. CONCLUSIONS: The phenotype of hepatocytes under in vivo and in vitro conditions has proven to be changeable from one to another.

Animals↗

[Surgical neoadjuvant chemo-hormonal therapy for advanced prostatic carcinoma].

To improve the therapeutic results as well as the patient's quality of life (QOL) in advanced prostatic carcinoma, total cystprostatectomy or pelvic exenteration was performed in combination with chemo-hormonal therapy before and after operation on twelve patients with stage D2 prostatic carcinoma who had infiltration in the periprostatic organs including urinary bladder and large intestine and showed strong bladder irritation, gross hematuria and ileus symptoms. Eight patients with severe cystic infiltration underwent total cystprostatectomy, urinary division and lymph node dissection, and four with ileus symptoms had pelvic exenteration, urinary division, proctostomy and lymph node dissection. As a rule of dosing schedule for chemo-hormonal therapy, 30-60mg/sq m of etoposide was continuously administered for 5 days before operation in addition to 250-500 mg of diethylbestrol diphosphate given for 30 days after operation. Furthermore, 2-3 courses of 30-60 mg/sq m of etoposide was administered for successive days, at 3-week intervals and then 30-60 mg/sq m of etoposide at 6-to-8-week intervals for 2 years together with 75-100 mg of chrolmadinone acetate as maintenance treatment. Nine of the 12 patients survived, including 4 patients with complete response, 3 patients with partial response and 2 patients with no change. These findings, suggested that the combination of surgical treatment and chemo-hormonal therapy is of use not only for providing an effective therapeutic means but also for improving the QOL in patients with advanced prostatic carcinoma.

Aged↗

[Reducing cross-talk in electrooculograms made with several electrodes].

In order to discuss how to handle the contralateral effect (cross-talk) when taking an electrooculogram (EOG) with two or more electrodes, a forced duction test was used to detect cross-talk potentials. The cross-talk potentials originating from the left eye were measured at the right eye for 5 subjects when the left eye was adducted and abducted alternately with a suction contact lens while the right eye was kept fixed. The cross-talk potentials detected at the right eye did not depend on the electrode position, but the contralateral EOG potentials depended on the electrode position around the left eye. The cross-talk value is calculated as the gain, 20.log [(cross-talk potential)/(contralateral EOG potential)]. The denominator of this expression considerably affects the gain since the contralateral potential depends on the position of the electrode. We propose that the effect of the cross-talk on the potential between a pair of electrodes can be cancelled with the gain value (-15.0dB: the mean value for the 5 subjects) when the contralateral electrode is set 20 mm from the outer canthus.

Electrodes↗

Detection of circulating intercellular adhesion molecule-1 in hepatocellular carcinoma.

Serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) were measured in 23 patients with chronic hepatitis (CH), 22 with liver cirrhosis (LC) and 45 with hepatocellular carcinoma (HCC) using an ELISA. Serum samples from all patients showed significantly higher cICAM-1 levels than serum from 50 normal controls. The cICAM-1 level was significantly increased in LC or HCC when compared with CH, but no differences were noted between LC and HCC. Levels of cICAM-1 correlated well with serum bilirubin, retention rate of indocyanine green, hyaluronic acid, type IV collagen 7-S and type III procollagen peptide levels but not with tumor size or circulating tumor markers (alpha-fetoprotein and des-gamma-carboxyprothrombin). Our findings indicate that the measurement of cICAM-1 is useful for the determination of the severity of liver disease and hepatic fibrosis. HCC tissues obtained from 10 patients were immunohistochemically stained for ICAM-1. Enhanced ICAM-1 expression was found on the tumor cell membranes. Sequential measurements of cICAM-1 levels showed that they changed in a similar manner to those of alpha-fetoprotein during the course of treatment of HCC in a patient with very high pretreatment levels of both markers. These results suggest that HCC cells shed ICAM-1 into the circulation. We conclude that cICAM-1 is not a diagnostic marker for HCC, but may be useful for monitoring the response to treatment.

Bilirubin↗

Tissue-specific molecular diversity of amidating enzymes (peptidylglycine alpha-hydroxylating monooxygenase and peptidylhydroxyglycine N-C lyase) in Xenopus laevis.

We investigated the molecular diversity of the paired enzymes, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidylhydroxyglycine N-C lyase (PHL), involved in peptide C-terminal amidation. Three kinds of amidating enzyme (AE) cDNAs (AE-I, AE-II and AE-III) have previously been isolated from Xenopus laevis skin. While AE-I cDNA encodes only PHM, AE-III cDNA encodes a protein containing both PHM and PHL sequences and a transmembrane domain. On the other hand, the translated product of AE-II has not been detected yet. Endoproteolytic cleavage of the AE-III protein generates separated forms of PHM and PHL that are purified from X. laevis skin. Expression of AE-III in insect cells using a baculovirus expression vector system indicated that PHM and PHL exist as a membrane-associated, bifunctional enzyme without endoproteolysis in insect cells. Both PHM and PHL activities were detected in all the X. laevis tissues examined. Particularly, the highest levels of both activities were found in skin, brain and heart. We identified basically three types of enzymes in X. laevis; soluble PHM, soluble PHL and a membrane-associated, bifunctional enzyme that has both PHM and PHL domains. While the skin contained soluble types of PHM and PHL, the brain and heart predominantly contained the membrane-associated, bifunctional type. Analysis of mRNA levels by the reverse-transcript polymerase chain reaction method and Western blot analysis using PHM-specific antibody revealed that such molecular diversity of PHM and PHL among the tissues are produced by changing the ratio of AE-I mRNA/AE-III mRNA, and by endoproteolytic processing of the membrane-associated precursor protein.

Amides↗

Heat and acid sensitivity of motile Aeromonas: a comparison with other food-poisoning bacteria.

The present study was undertaken to compare the heat and acid sensitivity of aeromonads with those of other food-poisoning bacteria. It became obvious that aeromonads were more sensitive to heat than Escherichia coli O157:H7, Staphylococcus aureus, and Salmonella typhimurium. Aeromonads were killed in peptone water within 2 min at 55 degrees C, while the other bacteria survived heating at 55 degrees C for more than 15 min. Aeromonas cells were also less resistant to heat in hamburger steaks. These findings suggest that Aeromonas infection can easily be prevented by heat treatment, although correct handling of food is required to avoid recontamination since aeromonads are very common in various kinds of food. E. coli, S. aureus and S. typhimurium cells survived in buffer at pH 3.2 and in foods seasoned with vinegar. By contrast, Aeromonas cells were found to be highly sensitive to acid. However, the resistance of Aeromonas to acid may be sufficient to allow it to infect the gastrointestinal tract since Vibrio parahaemolyticus, which causes numerous outbreaks of food-poisoning every year in Japan, was susceptible to acid to the same extent as Aeromonas.

Acetates↗

Functional expression and characterization of a Xenopus laevis peptidylglycine alpha-amidating monooxygenase, AE-II, in insect-cell culture.

The alpha-amidating reaction of peptide hormones is a two-step process which is catalyzed by peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidylhydroxyglycine N-C lyase (PHL). There are three types of mRNA for these amidating enzymes in Xenopus laevis, namely AE-I, AE-II and AE-III. AE-I encodes only PHM and AE-III encodes both PHM and PHL. AE-II seems to encode subtypes of both PHM and PHL. While AE-II mRNA is present in high amounts in frog skin, the actual enzymes originating from AE-II have not been detected. When we expressed AE-II in cultured insect-cells using the baculovirus expression vector system, the expressed enzyme was specifically localized to the membrane fraction due to its hydrophobic transmembrane domain. Alternatively, when the transmembrane-domain-deleted AE-II (Met1-Ile731) was expressed, the enzyme was secreted into the culture medium; this secreted enzyme was purified to homogeneity by a simple two-step procedure. We have verified that the reaction product of the purified enzyme was the amidated peptide, indicating that AE-II has the ability to catalyze the entire amidating reaction.

Amino Acid Sequence↗

Nucleus ventralis posteromedialis neurons relaying somatosensory lingual input to the cerebral cortex in the cat.

The cortical projection of somatosensory lingual units in the nucleus ventralis posteromedialis (VPM) of the thalamus was studied in urethane-chloralose anesthetized cats. Ipsilateral lingual units were recorded from the lateral subdivision of nucleus ventralis posteromedialis parvocellularis (VPMpcl). They were antidromically excited following electrical stimulation of the ventral aspect of the coronal gyrus or its caudally adjacent orbital gyrus. From these same cortical areas, positive surface potentials were recorded following electrical stimulation of the ipsilateral lingual nerve. Electrical stimulation of the same cortical areas elicited jaw opening movement. Contralateral somatosensory lingual units were recorded from the VPM proper. They were antidromically excited following electrical stimulation of the SI somatosensory cortex.

Animals↗

Expression of human thromboxane synthase using a baculovirus system.

Human thromboxane (TX) synthase (EC 5.3.99.5) was produced by the baculovirus expression system using cDNA encoding human TX synthase [(1991) Biochem. Biophys. Res. Commun. 78, 1479-1484]. A recombinant baculovirus TXS7 was expressed in Spodoptera frugiperda Sf9 insect cells. The expressed protein was recognized by monoclonal antibody, Kon 7 raised against human TX synthase [(1990) Blood 76, 80-85]. The recombinant TX synthase catalyzed the conversion of prostaglandin (PG) H2 to TXA2 and 12-hydroxy-heptadecatrienoic acid (HHT). Both conversions of PGH2 to TXA2 and HHT by the expressed TX synthase were completely inhibited by a specific TX synthase inhibitor, OKY-046 (5 microM).

Animals↗

Horizontal component of electro-oculogram as a parameter of arousal in dementia: relationship between intellectual improvement and increasing arousal under pharmacotherapy.

Although nootropics and metabolically active compounds sometimes attenuate intellectual deficits of dementia patients, this mechanism has not been discussed or investigated. The authors hypothesized that these compounds act to enhance attention and/or concentration by increasing the arousal level, and then improve intellectual functions. Based on this hypothesis, the authors investigated the arousal level and the improvement of intellectual functions in ten patients with Alzheimer type dementia and ten patients with multi-infarct dementia before and after 3 months pharmacotherapy using bifemelane hydrochloride. They then analyzed whether the increases in arousal level involves or relates to the improvement of intellectual functions. On the 20 patients, psychological tests were carried out, and the arousal level was evaluated using the frequency of rapid eye movements in the electro-oculogram (EOG) before and after 3 months administration of bifemelane hydrochloride. As a result, a significant positive correlation was observed between the improvement on the Hasegawa's dementia scale and the rate of increase in rapid eye movements in the EOG. The EOG monitoring can be a great help in establishing an objective evaluation method on drug efficacy.

Aged↗

Reduced isotope uptake restricted to the motor area in patients with amyotrophic lateral sclerosis.

To study degeneration in the central nervous system in amyotrophic lateral sclerosis (ALS), we studied four patients using single photon emission tomography (SPECT) and magnetic resonance imaging (MRI). MRI demonstrated high intensity along the pyramidal tract on T2-weighted images in two. SPECT demonstrated reduced isotope uptake restricted to the motor area. While the cause of degeneration of the cortical neurons in the motor area is unknown, SPECT is useful for detecting the degeneration in patients with ALS.

Amyotrophic Lateral Sclerosis↗

Ovariectomy increases the level of estrogen receptor mRNA and estrogen receptor binding sites in female rat adipose tissue.

The roles of estrogen in the changes in estrogen receptor (ER) mRNA and ER binding sites in rat adipose tissue were studied in female rats. To elucidate the mechanism(s) behind ovariectomy (OVX)-induced obesity, the levels of ER mRNA and ER binding sites in adipose tissue were analyzed three weeks after OVX using Northern blot analysis of ER mRNA and the [3H]E2 binding assay, respectively. OVX induced an increase in body weight, and replacement of estradiol (E2) prevented that increase. Significant increases in the amounts of ER mRNA and in [3H]E2-specific binding were observed after OVX, and E2 replacement reduced both of those increases. These results suggest that E2 may regulate rat obesity directly through ER in adipose tissues.

Adipose Tissue↗

Responders and non-responders to bifemelane hydrochloride in Alzheimer-type and multi-infarct dementia.

Although metabolically active compounds sometime attenuate cognitive deficits of dementia patients, this mechanism has not been discussed or investigated. We hypothesized that these compounds improve cognitive disorders not by directly acting on this cognitive function, but by increasing the arousal level. Based on this hypothesis, we investigated the change of arousal levels and the improvement of intellectual functions in 10 patients with Alzheimer-type dementia (ATD) and 10 patients with multi-infarct dementia (MID) before and 3 months after pharmacotherapy using bifemelane hydrochloride. For each patient, a psychological test battery was carried out and the arousal level was evaluated using the frequency of rapid eye movements in the electro-oculogram (EOG) and the frequency analysis of electroencephalogram (EEG) before and after the treatment. Evaluation of the cognitive improvement was made and eight out of the 20 patients were regarded as responders to the treatment. The frequency of small rapid eye movements (SREM) in the EOG increased significantly only in responders and the rate of change in SREM appearance in responders was significantly different from that in non-responders. This finding suggests that a part of the intellectual improvement in ATD and MID results from the increased level of arousal.

Aged↗