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H Adachi

Publications and source records attributed to H Adachi.

At least 181 records · Page 10Linked to original sources

Expression cloning of a novel scavenger receptor from human endothelial cells.

Scavenger receptors mediate the endocytosis of chemically modified lipoproteins, such as acetylated low density lipoprotein (Ac-LDL) and oxidized LDL (Ox-LDL), and have been implicated in the pathogenesis of atherosclerosis. The evidence that endothelial cells possess scavenger receptor activity is substantial, and this property is widely used in the isolation of endothelial cells from vascular tissues. In the current study, we have isolated, by expression cloning, the cDNA encoding a novel type of scavenger receptor expressed by endothelial cells (SREC), which mediates the binding and degradation of Ac-LDL. The primary structure of the molecule has no significant homology to other types of scavenger receptors, including the recently cloned endothelial cell Ox-LDL receptor, a member of the C-type lectin family. The cDNA encodes a protein of 830 amino acids with a calculated molecular mass of 85, 735 Da (mature peptide). Chinese hamster ovary cells stably expressing SREC bound 125I-labeled Ac-LDL with high affinity (Kd = 3.0 microg/ml, approximately 1.7 nM) and degraded them via an endocytic pathway. Association of DiII-Ac-LDL were effectively inhibited by Ox-LDL, malondialdehyde-modified LDL, dextran sulfate, and polyinosinic acid, but not by natural LDL and heparin. The cloned receptor has several characteristic domain structures, including an N-terminal extracellular domain with five epidermal growth factor-like cysteine pattern signatures and an unusually long C-terminal cytoplasmic domain (391 amino acids) composed of a Ser/Pro-rich region followed by a Gly-rich region.

Amino Acid Sequence↗

Synthesis and antimetastatic activity of L-iduronic acid-type 1-N-iminosugars.

L-Iduronic acid-type 1-N-iminosugars, (3R,4S,5R,6R)- and (3R,4S,5S,6R)-6-acetamido-4-amino-5-hydroxypiperidine-3-carboxylic acid (6 and 7, respectively), (3R,4S,5R,6R)-6-acetamido-4- guanidino-5-hydroxypiperidine-3-carboxylic acid (8), and (3R,4S,5R,6R)-4-amino- and -guanidino-5-hydroxy-6-(trifluoroacetamido) piperidine-3-carboxylic acid (9 and 10, respectively), were synthesized from siastatin B (1), isolated from Streptomyces culture, by the intramolecular Michael addition of O-imidate to its alpha,beta-unsaturated ester through cis oxiamination as a key step. Preincubation of B16 BL6 cells with these compounds inhibited invasion of the cells through reconstituted basement membranes. Pulmonary metastasis of B16 BL6 cells in mice was remarkably inhibited by pretreatment of the cells with these compounds in culture.

Animals↗

Dictyostelium IQGAP-related protein specifically involved in the completion of cytokinesis.

The gapA gene encoding a novel RasGTPase-activating protein (RasGAP)-related protein was found to be disrupted in a cytokinesis mutant of Dictyostelium that grows as giant and multinucleate cells in a dish culture. The predicted sequence of the GAPA protein showed considerable homology to those of Gap1/Sar1 from fission yeast and the COOH-terminal half of mammalian IQGAPs, the similarity extending beyond the RasGAP-related domain. In suspension culture, gapA- cells showed normal growth in terms of the increase in cell mass, but cytokinesis inefficiently occurred to produce spherical giant cells. Time-lapse recording of the dynamics of cell division in a dish culture revealed that, in the case of gapA- cells, cytokinesis was very frequently reversed at the step in which the midbody connecting the daughter cells should be severed. Earlier steps of cytokinesis in the gapA- cells seemed to be normal, since myosin II was accumulated at the cleavage furrow. Upon starvation, gapA- cells developed and formed fruiting bodies with viable spores, like the wild-type cells. These results indicate that the GAPA protein is specifically involved in the completion of cytokinesis. Recently, it was reported that IQGAPs are putative effectors for Rac and CDC42, members of the Rho family of GTPases, and participate in reorganization of the actin cytoskeleton. Thus, it is possible that Dictyostelium GAPA participates in the severing of the midbody by regulating the actin cytoskeleton through an interaction with a member of small GTPases.

Amino Acid Sequence↗

cDNA cloning and expression of chicken aminopeptidase H, possessing endopeptidase as well as aminopeptidase activity.

Chicken aminopeptidase H is a cysteine protease possessing endopeptidase as well as aminopeptidase activity [Rhyu, M. R., Nishimura, T., Kato, Y., Okitani, A. & Kato, H. (1992) Eur. J. Biochem. 208, 53-59]. This enzyme exhibits molecular masses of 400 kDa on gel filtration and 52 kDa on SDS/PAGE, indicating that it consists of eight subunits with the same molecular mass. In the current study, we cloned the cDNA for the catalytic subunit of chicken aminopeptidase H. The open reading frame of the aminopeptidase H gene consists of 1362 base pairs encoding a 52-kDa protein consistent with the molecular mass determined on SDS/PAGE; the deduced amino acid sequence contains all the partial sequences determined for the purified enzyme. The sequence is similar to that of the bleomycin hydrolase of rabbit lung, which has been partially determined. The recombinant 52-kDa protein expressed in COS7 cells exhibited both aminopeptidase and endopeptidase activities, which were inhibited by monoiodoacetic acid. Furthermore, the expression of aminopeptidase H in COS7 cells was also recognized on immunoblotting. This gene is the first one for aminopeptidase H in an animal tissue whose sequence has been completely determined.

Amino Acid Sequence↗

Differential tissue distribution of the beta- and gamma-subunits of human cytosolic platelet-activating factor acetylhydrolase (isoform I).

The cDNA for human platelet-activating factor acetylhydrolase (PAF-AH) beta-subunit was cloned. The complete amino acid sequence deduced from cDNA contains 229 amino acids and is completely identical with that of the bovine subunit. Moreover, the sequence of the human beta-subunit protein shows 62.4% identity with the human gamma-subunit at the amino acid level. Southern blot analysis suggested the presence of multiple genes and we indeed found another closely related pseudo gene. Northern blot analysis showed that the 4.0 kb transcript was expressed in all tissues tested, suggesting the ubiquitous distribution of the subunit protein. Differential distribution of beta- and gamma-subunits might suggest that the oligomeric structure of PAF-AH is different from tissue to tissue.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Resolution of protein-losing hypertrophic gastropathy by eradication of Helicobacter pylori.

UNLABELLED: There is as yet no consensus about the need for treatment of Helicobacter pylori infections, except for H. pylori-associated peptic ulcer. We present a 3-year-old boy with a 3-month history of oedema and hypoproteinaemia associated with hypertrophic gastropathy. Abdominal scintigram using intravenous 99mTc-labelled human serum albumin scintigraphy and direct measurement of protein in gastric juice proved that serum proteins were massively secreted in the stomach. Histological findings of mucosal inflammation were observed and H. pylori was isolated from the gastric mucosa. The protein loss promptly stopped within 2 weeks of the beginning of eradication therapy. CONCLUSION: Protein-losing hypertrophic gastropathy may be induced by Helicobacter pylori-associated gastritis and should therefore be carefully evaluated by histological and bacteriological examination to provide a basis for eradication of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Nitric oxide production during exercise in chronic heart failure.

In chronic heart failure (CHF), the ventilatory response is increased compared with normal. This response is, in part, caused by reduced perfusion to ventilated lung. Nitric oxide (NO) is a potent vasodilator and may have an important role in pulmonary vasodilatation during exercise. NO is present in exhaled air. The amount of NO in exhaled air, when breathing NO-free compressed air, is known to increase in normal subjects during exercise. In this study, we quantified NO output in exhaled air in patients with CHF during exercise. Six patients with CHF (New York Heart Association Class II and III; two with dilated cardiomyopathy, three with ischemic heart disease, and one with hypertensive heart disease) and six normal subjects were studied with a symptom-limited incremental exercise test on a cycle ergometer. Oxygen uptake (VO2), carbon dioxide output (VCO2), and minute ventilation (VE) were measured breath by breath with a mass spectrometer, flow meter, and computer. The NO concentration was continuously measured in mixed expired air by chemiluminescence. Peak exercise work rate was lower in patients with CHF than in normal subjects (71.3 +/- 41.6 W vs 257.0 +/- 49.7 W; p < 0.01). Patients with CHF showed a higher VE/VCO2 level at peak exercise than normal subjects (CHF, 47.0 +/- 10.7; normal subjects, 35.6 +/- 5.2; p < 0.01). NO concentration of exhaled air at rest was lower in CHF patients than in normal subjects (4.0 +/- 2.2 ppb vs 10.5 +/- 6.2 ppb, respectively; p < 0.05). NO output from the respiratory tract (VNO) was significantly lower in patients with CHF compared with normal subjects at rest (45.3 +/- 24.3 nl/min, 117.5 +/- 60.1 nl/min, respectively, p < 0.05), and although it increased during exercise, it did not increase in patients with CHF as much as in normal subjects (75.3 +/- 43.4 nl/min vs 512.9 +/- 253.6 nl/min, respectively; p < 0.01). The increase above rest (exercise/rest) was smaller in patients with CHF than in normal subjects (2.10 +/- 1.92 vs 4.81 +/- 2.67, p < 0.05). These data support the concept that the smaller increase in NO production (VNO) during exercise may be responsible for a blunted vasodilation in patients with CHF, resulting in a smaller reduction in dead space/tidal volume and VE/VCO2 at the lactic acidosis threshold than normal. This finding may play a role in the abnormally high ventilatory response to exercise in patients with CHF.

Adult↗

Immunohistochemical demonstration of cytokeratin in human embryonic neurons arising from placodes.

Sensory neurons of the olfactory, trigeminal, facial, vestibulo-cochlear, glossopharyngeal and vagal nerves, and neurons migrating along the olfactory nerve to the brain have special anlagen, made up of placodes located in the epithelial layer. To investigate the characteristic phenotype of placode-derived neurons, immunohistochemical analysis of intermediate filaments was conducted on formalin-fixed human embryonic tissues. Neurons arising from placodes including luteinizing-hormone releasing hormone (LHRH) neurons migrating from the olfactory placode to the brain had immunoreactivity to antibodies specific to cytokeratin, AE1 and CAM5.2 during the embryonic stage. However, this immunoreactivity disappeared during the late embryonic to the post-embryonic stage and was not observed in the roots of these nerves in the post-natal stage. Immunoreactivity was detected in both the somata and processes, and the distribution differed from that described in rodent brain neurons. With this exception, no other human peripheral neurons, including spinal dorsal root ganglia, had immunoreactivity with anti-cytokeratin antibodies throughout the entire developmental stage. Although the cephalic neural crest also directly generates neurons to most of the cranial sensory ganglia, we could not find any evidence that it contributed to the genesis of cytokeratin-positive embryonic neurons. We concluded that cytokeratin is an intermediate filament common to human embryonic neurons of cephalic placodal origin and that this immunohistochemical marker may be useful in analyzing the developmental sequence of several congenital diseases involving the cranial nerves, such as Moebius syndrome and Goldenhar syndrome.

Adult↗

Effects of bisphosphonates on alkaline phosphatase activity, mineralization, and prostaglandin E2 synthesis in the clonal osteoblast-like cell line MC3T3-E1.

The effects of 3 bisphosphonates, AHBuBP, AHPrBP, and Cl2MBP on cell growth, alkaline phosphatase (ALP) activity, mineralization, and prostaglandin E2 (PGE2) synthesis in the clonal osteoblast-like cell line MC3T3-E1 were studied. These bisphosphonates had essentially similar effects on growth and the osteoblastic functions of the cells, i.e., they had no inhibitory effects on cell growth except at higher concentrations, they increased ALP activity, and inhibited PGE2 production. In the presence of AHBuBP, ALP activity was higher than that in the control after day 6 of culture. Lower concentrations of AHBuBP slightly facilitated mineralization by the cells. It is probable that bisphosphonates enhance the functions of osteoblasts in certain concentration and that the inhibition of endogenous PGE2 production may be involved in the mechanism of action of bisphosphonates.

Alendronate↗

Effect of oral administration of prostaglandin E1 on erectile dysfunction.

OBJECTIVES: To investigate the effect of limaprost, an oral prostaglandin E1 (PGE1) derivative, on erectile dysfunction and to compare the effects of limaprost with a Chinese herbal drug, gosyajinki-gan. PATIENTS AND METHODS: The study comprised 50 consecutive patients with mild erectile dysfunction who showed a good erectile response to intracavernosal injection with 20 micrograms of PGE1. Limaprost was administered to the first 25 patients (30 micrograms three times daily) and gosyajinki-gan (7.5 g three times daily) to the next 25 patients, for 8 consecutive weeks. Patients were evaluated by their ability to achieve vaginal penetration and by a subjective assessment of erectile function (penile rigidity and maintenance of erection) before and after the treatment, using a self-administered questionnaire. Objective measurements (nocturnal penile tumescence, NPT, values) were also evaluated. RESULTS: Eleven of the 24 patients who received limaprost without interruption and four of the 24 taking gosyajinki-gan succeeded in vaginal penetration; the difference in the positive response rate was significant. The mean increment of NPT was significantly higher with limaprost treatment. However, all positive responders in both groups did not experience a full erection. There were no side-effects in any patient except one in the limaprost group who developed a facial flush. Thus the treatment was mild enough to be tolerated. CONCLUSION: Limaprost was more effective for mild erectile dysfunction than was gosyajinki-gan.

Administration, Oral↗

Continuous brachial plexus infusion of butorphanol-mepivacaine mixtures for analgesia after upper extremity surgery.

We have recently reported that continuous administration of butorphanol into the brachial plexus neurovascular sheath provided superior analgesia compared with that obtained with continuous i.v. administration. Furthermore, we found that analgesia was most pronounced when a mixture of mepivacaine and butorphanol was given and that butorphanol alone ranked next. In this study, we increased the dose of butorphanol, compared with that used in our previous reports, and an initial bolus dose of butorphanol was administered into the brachial plexus neurovascular sheath just after surgery had ended. Thereafter, postoperative pain relief was estimated. In patients undergoing upper extremity surgery with continuous axillary brachial plexus block, group A received a bolus of 1 ml of physiological saline with 1.5% mepivacaine, 10 ml into the brachial plexus sheath followed by a continuous brachial plexus infusion of 0.5% mepivacaine with butorphanol 6 mg at a rate of 144 ml/ 72 h. Group B was given a bolus of butorphanol 1 mg (1 ml) with 1.5% mepivacaine, 10 ml into the brachial plexus sheath and a continuous brachial plexus infusion of 0.5% mepivacaine with butorphanol 6 mg at a rate of 144 ml/72 h. After operation, VAS scores did not differ between the two groups. The time to first use of supplementary analgesia did not differ significantly between the two groups and there were no significant differences in the number of patients who required supplementary analgesia. These results indicate that continuous butorphanol 2 mg day-1 with 0.5% mepivacaine provided sufficient postoperative analgesia after upper limb surgery.

Analgesia↗

Effects of a new cardiotonic phosphodiesterase III inhibitor, olprinone, on cardiohemodynamics and plasma hormones in conscious pigs with heart failure.

We examined the effects of a novel phosphodiesterase III inhibitor, olprinone, on the cardiohemodynamics and plasma hormones in conscious pigs with pacing-induced heart failure. After pacing for 5-10 days, cardiac output (CO) decreased from 2.25 +/- 0.17 to 1.67 +/- 0.13 L/min (n = 8, p < 0.01) and stroke volume (SV) decreased from 20.1 +/- 2.1 to 12.0 +/- 1.6 ml (n = 8, p < 0.01), whereas left arterial pressure (LAP) increased from 2.8 +/- 1.2 to 16.7 -/+ 0.9 mm Hg (n = 7, p < 0.001) and systemic vascular resistance (SVR) increased from 38.7 +/- 3.5 to 49.8 +/- 4.2 mm Hg/L/min (n = 8, p < 0.01). Sequential intravenous infusions of 0.03, 0.3, and 3.0 microg/kg/min of olprinone at 30-min intervals to eight pigs caused dose-dependent increases in the decreased CO, SV, and maximal rate of rise in left ventricular pressure (LV dP/dt(max)) and decreased the elevated LAP and SVR. Olprinone at 3.0 microg/kg/min maximally increased CO, SV, and LV dP/dt(max) by 40.0 +/- 10.8% (p < 0.05 vs. vehicle), 25.6 +/- 6.9% (p < 0.05), and 43.9 +/- 11.2% (p < 0.01), respectively, and brought about a slight increase in heart rate and decreases in LAP and SVR, by 35.9 +/- 7.3% (p < 0.001) and 27.9 +/- 4.8% (p < 0.01), respectively. Olprinone did not affect the rate-pressure product. In addition, olprinone produced significant decreases in the plasma levels of atrial natriuretic peptide and cyclic guanosine monophosphate, with no changes in the plasma levels of cyclic adenosine monophosphate and catecholamines or plasma renin activity. These findings indicate that the short-term intravenous infusions of olprinone ameliorated the decreased left ventricular function without affecting myocardial oxygen consumption or the sympathetic nervous system in conscious pigs with heart failure.

3',5'-Cyclic-AMP Phosphodiesterases↗

Adequacy of pacing rate during exercise in rate responsive ventricular pacing.

Our objective was to determine the adequate pacing rate during exercise in ventricular pacing by measuring exercise capacity, cardiac output, and sinus node activity. Eighteen patients with complete AV block and an implanted pacemaker underwent cardiopulmonary exercise tests under three randomized pacing rates: fixed rate pacing (VVI) at 60 beats/min and ventricular rate-responsive pacing (VVIR) programmed to attain a heart rate of about 110 beats/min or 130 beats/min (VVIR 110 and VVIR 130, respectively) at the end of exercise. Compared with VVI and VVIR 130, VVIR 110 was associated with an increased peak oxygen uptake (VVIR 110: 20.3 +/- 4.5 VVI: 16.9 +/- 3.1; P < 0.01; and VVIR 130: 19.0 +/- 4.1 mL/min per kg, respectively; P < 0.05 and a higher oxygen uptake at anaerobic threshold (15.3 +/- 2.7, 12.7 +/- 1.9; P < 0.01, and 14.6 +/- 2.6 mL/min per kg; P < 0.05). The atrial rate during exercise expressed as a percentage of the expected maximal heart rate was lower in VVIR 110 than in VVI or VVIR 130 (VVIR 110: 75.9% +/- 14.6% vs VVI: 90.6% +/- 12.8%; P < 0.01; VVIR 110 vs 130: 89.1% +/- 23.1% P < 0.05). There was no significant in cardiac output at peak exercise between VVIR 110 and VVIR 130. We conclude that a pacing rate for submaximal exercise of 110 beats/min may be preferable to that of 130 beats/min in respect to exercise capacity and sympathetic nerve activity.

Cardiac Output↗

Cloning of the human orphan receptor germ cell nuclear factor/retinoid receptor-related testis-associated receptor and its differential regulation during embryonal carcinoma cell differentiation.

We have cloned a cDNA encoding the full-length coding region of the human homologue of the germ cell nuclear factor (GCNF)/retinoid receptor-related testis-associated receptor (RTR), from a human testis cDNA library. The amino acid sequence of human GCNF/RTR is highly homologous to that of the mouse GCNF/RTR. The largest difference between the two homologues is a 15 amino acid deletion in the human GCNF/RTR at amino acid 47. The GCNF/RTR gene was localized on human chromosome 9. Northern blot analysis using poly(A)+ RNA from different human tissues showed that GCNF/RTR mRNA is most abundantly expressed in the testis. GCNF/RTR was also highly expressed in embryonic stem cells and embryonal carcinoma cells but repressed in its differentiated derivatives. Induction of differentiation of mouse embryonal carcinoma F9 cells and human embryonal carcinoma NTERA-2 clone D1 (NT2/D1) cells by all-trans retinoic acid was accompanied by a down-regulation of GCNF/RTR. Our observations suggest that GCNF/RTR plays a role in the control of gene expression in early embryogenesis and during spermatogenesis.

Amino Acid Sequence↗

New method for the evaluation of the response of cultured cell lines to continuous low-dose-rate irradiation from encapsulated iridium-192 seeds with hyperthermia.

A new method was designed to investigate and evaluate the biological effectiveness of hyperthermia combined with continuous low-dose-rate irradiation (CLDRI) from encapsulated iridium-192 seed sources on glioma cells in vitro using the MTT assay. The system consists of 10 iridium seeds contained in a catheter bent into a circle, which is placed on a culture plate containing the cells. The effects of CLDRI and CLDRI combined with hyperthermia on a cultured rat glioma cell line (C-6) were studied. The number of surviving cells decreased as the total radiation dose increased. There was no significant difference in survival rates at dose rates of 0.1 Gy/hr and of 0.2 Gy/hr (p = 0.2811). An additive effect was observed in the cells treated with hyperthermia at 41 degrees C and 42 degrees C, combined with CLDRI, and synergistic effect between the two treatment modalities was observed at 43 degrees C. This new device is less expensive, easily reproducible, and can also be performed easily enough to examine a large number of samples in a short time period for sensitivity testing.

Animals↗

Hyperinsulinemia and the development of ST-T electrocardiographic abnormalities. An 11-year follow-up study.

OBJECTIVE: It has been suggested that insulin resistance and consequent hyperinsulinemia promote atherosclerosis, but few prospective studies have reported the relationships between hyperinsulinemia and the development of ST-T abnormalities in the 12-lead resting electrocardiogram (ECG) in populations in which atherosclerosis is rare. RESEARCH DESIGN AND METHODS: A total of 304 Japanese men and women, aged 20-69 years, selected for having high blood glucose or more than a trace-positive urine glucose from a population-based health examination in 1981, were followed for 11 years. Of these, 33 died, 1 from myocardial infarction, while 260/271 living were reexamined in 1992. The 237 subjects with a normal ECG at the baseline examination were analyzed. RESULTS: Incident ST-T abnormalities occurred in 13/237 people. Insulin concentrations were positively associated with the development of ST-T abnormalities (relative risk approximately 8, comparing those in the highest versus lowest quartile of insulin values). Adjustment for age, sex, and systolic blood pressure or other risk factors had little effect on this relationship. CONCLUSIONS: Hyperinsulinemia was related to the development of ST-T abnormalities in ECGs in the absence of the development of clinical signs of atherosclerosis, independent of blood pressure and other risk factors in men and women with mild glucose intolerance.

Adult↗

[Long-term clinical course of Peyronie's disease treated conservatively].

BACKGROUND: To evaluate the natural history of Peyronie's disease and to determine the suitable time for surgical treatment, we investigated changes of clinical findings of the disease over time. PATIENTS AND METHODS: We evaluated changes of plaque size, penile curvature and erectile dysfunction in 10 patients with Peyronie's disease. The mean follow-up period was 36.8 months. RESULTS: At the first examination, the mean plaque size of patients with erectile dysfunction was larger than that of those without erectile dysfunction, suggesting a positive association between size and erectile function. There was no significant relationship between plaque size and penile pain or penile curvature. The mean size of plaques decreased significantly compared with that at the first examination (p < 0.05). However, penile curvature, pain and erectile dysfunction persisted during the follow-up period in all but one patient, who showed improvement of penile curvature. CONCLUSION: These results suggest that we may recommend a shorter observation period until surgery that we have done for some patients who want to be surgically treated.

Adult↗