Search PubMed⌕ Search

Biomedical subjects

H Adachi

Publications and source records attributed to H Adachi.

At least 343 records · Page 19Linked to original sources
PubMed1992

Improved transdermal delivery of prostaglandin E1 through hairless mouse skin: combined use of carboxymethyl-ethyl-beta-cyclodextrin and penetration enhancers.

The optimal prescription of transdermal preparations of prostaglandin E1 (PGE1) for treatment of peripheral vascular diseases has been investigated. The chemical stability of PGE1 in fatty alcohol/propylene glycol (FAPG) ointment was markedly improved by carboxymethyl-ethyl-beta-cyclodextrin (CME-beta-CyD). Application of a PGE1 ointment containing the penetration enhancer, 1-dodecylazacycloheptane-2-one (Azone) or 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), onto the skin of hairless mice showed the increase of blood flow in the skin due to the vasodilating action of PGE1. In particular, the ointment containing a PGE1-CME-beta-CyD complex supplemented with HPE-101 showed the most prominent increase of the blood flow. Compared with other ointments, this ointment was found to show significantly greater transfer of HPE-101 into in-vitro preparations of the skin of hairless mice. Transfer of PGE1 into the skin was thought to be facilitated by this increased transfer of HPE-101. These results suggest that a combination of CME-beta-CyD and HPE-101 is useful for designing PGE1 ointments for topical application with good chemical stability and percutaneous permeability.

Administration, Cutaneous↗
PubMed1992

Assignment of the human renal dipeptidase gene (DPEP1) to band q24 of chromosome 16.

Renal dipeptidase (DPEP1) or dehydropeptidase-I (E.C.3.4.13.11) is a kidney membrane enzyme which hydrolyzes a variety of dipeptides. DPEP1 is implicated in the renal metabolism of glutathione and its conjugates and is also responsible for hydrolysis of beta-lactam antibiotics. Using a human DPEP1 cDNA probe, we mapped the human renal dipeptidase gene to human chromosome 16 at band q24 by in situ hybridization.

Chromosome Banding↗
PubMed1992

Evaluation of biplane color Doppler transesophageal echocardiography in 200 consecutive patients.

BACKGROUND: We developed the first biplane transesophageal echocardiography (TEE) probe with two orthogonal transducers, allowing synchronous side-by-side displays of the heart on a monitor TV, and compared its diagnostic value with that of conventional single-plane TEE using commercially available Doppler equipment in 200 consecutive patients intraoperatively, perioperatively, or on an outpatient basis. METHODS AND RESULTS: Insertion was easy, except in one patient with a mediastinal tumor, and no complications were encountered. Both transverse and longitudinal scans allowed correct identification of true and false lumina in all 30 aortic dissection examinations, but longitudinal scanning was slightly superior in detecting types I and III entry sites. Three entries that were not detected by transverse scanning (two of DeBakey type I and one of type III) were visualized by longitudinal scanning. Among 37 cases of mitral regurgitation (MR), longitudinal scans were significantly superior (p less than 0.05) in revealing multiple jets (nine compared with two with transverse scanning). Although both planes yielded almost identical mean values for the maximum jet areas, a difference of over 50% in jet area size on the two planes was observed in 19 cases. The measured jet areas showed significant correlation with the angiographic MR grading, especially for the larger of the biplane measurements (p less than 0.01), and different grades showed little overlap. Longitudinal images increased the acoustic window of the heart and aorta from the esophagus. Moreover, longitudinal scanning provided good visualization of both ventricular outflow tracts, the ascending aorta, main pulmonary artery, and superior vena cava. CONCLUSIONS: This modality greatly facilitates a three-dimensional comprehension of cardiovascular lesions and flow dynamics, especially in aortic dissection and MR, and its safety was demonstrated. Our data demonstrate the usefulness of this new technique in comparison with conventional single-plane TEE.

Aortic Dissection↗
PubMed1992

Cardiac output-O2 uptake relation during incremental exercise in patients with previous myocardial infarction.

BACKGROUND: The cardiac output-O2 uptake (VO2) relation, which is thought to be linear and predictable in normal humans, has not been clarified in cardiac patients. We evaluated the relation between cardiac output and VO2 during the incremental exercise test in patients with previous myocardial infarction. METHODS AND RESULTS: Twenty-two patients (age, 58.1 +/- 8.0 years) with previous myocardial infarction performed a symptom-limited exercise test on a cycle ergometer. VO2 was calculated from the expired gas analysis, and cardiac output was measured by a computerized cadmium telluride detector every 10 seconds during exercise. The ratio of increase in VO2 to the increase in work rate (delta VO2/delta WR) below and above the anaerobic threshold (AT) was 11.1 +/- 3.6 and 11.1 +/- 2.9 ml/min/W, respectively, showing no significant difference. However, the ratio of increase in cardiac output to increase in work rate (delta CO/delta WR) below the AT was 50.1 +/- 26.6 ml/min/W and was significantly decreased to 11.8 +/- 25.3 ml/min/W above the AT (p = 0.0002). The decreased delta CO/delta WR above the AT primarily would be due to silent myocardial ischemia produced by exercise, as there was the presence of 201Tl redistribution in 15 of 16 patients in whom myocardial 201Tl scintigraphy with dipyridamole or exercise stress testing was evaluated. delta CO/delta VO2, which has been reported to be approximately 5.5 in normal subjects, was only 4.4 +/- 2.6 at work rates below the AT and was decreased to 1.1 +/- 2.3 at work rates above the AT. CONCLUSIONS: The relation between cardiac output and VO2 during exercise in patients with previous myocardial infarction differs profoundly from that reported in normal subjects. These findings must be considered when we noninvasively estimate the change in cardiac output during exercise by obtaining VO2 in patients with coronary artery disease.

Adult↗
PubMed1992

Thrombolytic effects of a novel modified tissue plasminogen activator, E6010, on coronary thrombosis in the pig.

This study was conducted to compare the thrombolytic effect of a novel modified tissue plasminogen activator, E6010, with that of recombinant human tissue plasminogen activator (t-PA), administered by single intravenous bolus injection in pigs with occlusive coronary thrombosis. Thrombosis was induced by electrical stimulation of the intimal surface of the left circumflex coronary artery. Coronary blood flow velocity and hemodynamic parameters were observed for 1 hr after complete cessation of coronary flow. Ten minutes after heparin injection (300 U/kg), E6010, t-PA or placebo was intravenously administered as a bolus. E6010 at 0.2 and 0.4 mg/kg caused recanalization of the occluded coronary artery in 1 of 6 and 5 of 5 pigs, respectively. The time to recanalization after 0.4 mg/kg of E6010 was 22 +/- 11 min (mean +/- S.E.M.). t-PA (0.4 mg/kg) caused recanalization in only 1 of 5 pigs. Recanalization did not occur in any of the 6 animals administered placebo. Plasma clearance of E6010 was smaller than that of t-PA (4.9 +/- 0.3 vs. 9.4 +/- 3.8 ml/min/kg). There were no significant differences in plasma levels of fibrinogen, alpha 2-plasmin inhibitor and plasminogen among the placebo, E6010 and t-PA groups. These results suggest that the slower clearance of E6010 from plasma contributes to the effective thrombolytic action of E6010 following single intravenous bolus injection.

Animals↗
PubMed1992

Inhibitory effect of a novel antianginal agent, E4080, on ST segment elevation induced by vasopressin in anesthetized guinea pigs.

We compared the antianginal effect of E4080, a novel bradycardiac agent with coronary vasodilating properties, with those of a bradycardiac agent and some coronary vasodilators in vasopressin-induced anginal model of guinea pigs. An i.v.-administration of vasopressin (0.2 IU/kg) produced an ST segment elevation on electrocardiograms (ECG) of 0.30 +/- 0.05 mV from the baseline within 30 sec in anesthetized guinea pigs. The ST segment elevation on ECG was used as an index of myocardial ischemia. E4080 and other drugs were injected i.v. 5 min before the administration of vasopressin. E4080 at 5 mg/kg depressed the ST segment elevation induced by vasopressin to 0.06 +/- 0.01 mV (20% of control, n = 6, P < 0.001). However, alinidine (5 mg/kg), which produced the same bradycardic action (reduction of heart rate by 50%) as that of E4080, tended to inhibit the ST segment elevation, but this was not statistically significant. On the other hand, other vasodilators such as isosorbide dinitrate (0.3 mg/kg), nifedipine (0.1 mg/kg) and lemakalim (1 mg/kg) also significantly reduced the ST segment elevation to 0.16 +/- 0.03, 0.08 +/- 0.04 and 0.09 +/- 0.03 mV, respectively. These results suggest that the inhibitory effect of E4080 on the ST segment elevation induced by vasopressin is due to the coronary vasodilating effect rather than the bradycardiac effect, and that E4080 would be useful as an antianginal agent.

Anesthesia↗
PubMed1992

Inhibitory effect of prostaglandin E1 on laurate-induced peripheral vascular occlusive sequelae in rabbits: optimized topical formulation with beta-cyclodextrin derivative and penetration enhancer HPE-101.

Prostaglandin E1 (PGE1) and its inclusion complexes with beta-cyclodextrin (beta-CyD) and O-carboxymethyl-O-ethyl-beta-cyclodextrin (CME-beta-CyD) were made as topical preparations. The PGE1 preparations, when applied with a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), markedly increased the regional blood flow in the ear of rabbits and were longer acting than when administered by the intravenous route. Topical application of the PGE1 preparations significantly protected rabbits against laurate-induced peripheral vascular occlusive sequelae; the protective potency increased in the order of PGE1 alone = beta-CyD complex < CME-beta-CyD complex preparation. The PGE1 preparations elicited skin reactions such as erythema and oedema depending on their vasodilating actions. These reactions disappeared gradually after removal of the preparations, and hence may not be serious obstacles for their safe use. These results suggest that combinations of CME-beta-CyD and HPE-101 work synergistically to facilitate the entry of PGE1 into the skin, and consequently enhance the therapeutic potential of PGE1 in the topical preparation tested.

Administration, Topical↗
PubMed1992

Outcome of Stanford type B acute aortic dissection.

BACKGROUND: The optimal timing of surgery in patients with Stanford type B aortic dissection remains controversial. This report reviews retrospectively early and long-term outcomes of patients with Stanford type B acute aortic dissections at our institute. METHODS AND RESULTS: From April 1979 through January 1991, 75 patients were diagnosed with Stanford type B aortic dissection, and 58 of them were hospitalized within 2 weeks from onset. They were treated initially as follows: emergent surgery was performed in 13 patients for rupture or impending rupture, and the remaining 45 were treated medically. In the former group, nine patients (69%) died; in the latter, eight (18%) needed surgery because of enlargement or rupture of the aneurysm in the follow-up period, and only one of these (13%) died. Of the other 37 patients treated medically, three (8%) died within 2 weeks and seven died (19%) in the chronic phase, four of them from rupture. Among 42 discharged patients initially treated medically, rupture occurred in 11.9% (five of 42). CONCLUSIONS: In acute-phase cases, surgical mortality is so high that medical treatment is preferable unless there are major complications. However, even in patients who had undergone successful initial medical treatment, expansion of the aneurysm, requiring surgery, often occurred. If careful observation reveals any sign of expansion, because elective surgery can be performed at low risk, it should be considered as soon as possible before a rupture develops.

Actuarial Analysis↗
PubMed1992

Intraoperative echocardiography for diagnosis and treatment of aortic dissection. Utility of color flow mapping for surgical decision making in acute stage.

In the past eight years until July 1992, 92 patients were admitted in the acute state of aortic dissection within two weeks from the onset of symptoms. 41 were diagnosed as Stanford type A and 51 were type B by transthoracic and transesophageal echography, computer tomography, and surgery. Sensitivity of transesophageal echography to detect the intimal flap and the false lumen was 97.6% in patients with Stanford type A and 100% in patients with Stanford type B. The surgical decision making has been mostly depending on the transesophageal echographic diagnosis. When the intimal flap was detected in the ascending aorta (Stanford type A) surgery was performed in emergency regardless of any evidence of rupture, cardiac tamponade, and severe aortic regurgitation. When the aortic dissection was detected only in the descending aorta (Stanford type B) the main course of therapeutic strategy in our institute was medical treatment. Surgery was performed on 37 patients of type A and nine patients of type B with mortality of 18.9% and 55.5% respectively. Four patients of type A and 42 patients of type B were treated medically with a mortality of 75.0% and 2.2% respectively. The relatively large leakages from the anastomosis of the aortic clamp site were repaired secondarily in two patients, and fenestration of the superior mesenteric artery was performed on one patient due to ischemia of the small intestine depending on the intraoperative direct scanning of color flow mapping. Coronary artery involvement of dissection was strongly suspected in two patients by intraoperative transesophageal echography and aortocoronary bypass grafting was performed on these patients. Perfusion problems was encountered in five of 37 patients with type A aortic dissection (13.5%) during cardiopulmonary bypass. Intraoperative transesophageal echography could clearly detect the hemodynamic changes in the descending aorta resulting from inadequate perfusion which was useful for the management of perfusion control during cardiopulmonary bypass. Secondary repair of the aortic arch was required due to ischemia of the aortic arch vessels in two patients after the primary surgery. The extension of the dissection into the aortic arch vessels can be promptly diagnosed with the combination of transesophageal echography and transcutaneous echography. In conclusion, transesophageal Doppler echography is the most rapid diagnostic tool for decision making in acute aortic dissection, and intraoperative transesophageal echo can provide useful information to resolve the perfusion difficulties during cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1992

[A clinical experience of V-A bypass using a new antithrombotic coating material].

To perform V-A bypass with minimal systemically administered heparin, we used a equipment coated by fluorine-acryl-styrene-urethane-silicone graft copolymer. A 67 year old woman developed right heart failure after CABG was treated for 25 hours on V-A bypass without oxygenator by using this new antithrombotic coating material. During V-A bypass, hemodynamics were stable. Not coagulative nor hemolytic disorder was observed. And she did not suffer from thrombotic nor hemorrhagic complications. Scanning electron microscopy of coated equipment demonstrated only minor deposits on the surface, and morphologic study of platelet was almost normal. By using this new antithrombotic material it is possible to perform V-A bypass with minimal heparinization, thus avoiding the risk of major coagulation complications.

Acrylates↗
PubMed1991

Involvement of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vitro.

Although transforming growth factor (TGF) alpha and epidermal growth factor (EGF) receptor (EGFR) autocrine mechanism is widely demonstrated in many kinds of cancers, its biological significances still remain circumstantial. We critically assessed the significance of this mechanism on the growth of an ovarian cancer cell line. Northern blot analysis in polyadenylated RNA isolated from cells by using 32P-labeled pre-TGF alpha, EGRF, and prepro-EGF complementary DNAs as probes revealed that pre-TGF alpha and EGFR but not prepro-EGF gene transcripts were expressed in the cell. TGF alpha and EGFR but not EGF proteins were observed by immunocytochemical stainings, using monoclonal antibodies against human TGF alpha, EGFR, and EGF, respectively. This cell line possessed a class of high affinity EGF receptor by 125I-EGF binding studies; Kd being 2.9 x 10(-10) M and Bmax to be 7.7 x 10(4) sites/cell. As much as 1.12 +/- 0.14 ng (SD; n = 3)/10(7) cells/24 h of TGF alpha was secreted in the conditioned media. These results suggested the expression of a TGF alpha/EGFR autocrine mechanism in this cell line. We, therefore, assessed the biological significance of this mechanism on the growth of this cell line in serum-free monolayer cell cultures. Although 0.1, 1.0, and 10 nM concentrations of TGF alpha did not show significant growth promotion, monoclonal antibodies against TGF alpha and EGFR but not EGF significantly inhibited cell growth. All these data suggested the biological importance of a TGF alpha/EGFR autocrine mechanism on the growth of this cell line in vitro.

Antibodies, Monoclonal↗
PubMed1991

Importance of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vivo.

We have elucidated the importance of a transforming growth factor (TGF) alpha and epidermal growth factor receptor autocrine mechanism on the growth of a human ovarian serous cystadenocarcinoma-derived cell line (SHIN-3) in vitro. In this study, we studied the biological significance of this autocrine mechanism in vivo using female athymic nude (nu/nu) mice. We measured the mouse plasma epidermal growth factor and TGF alpha levels by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Plasma epidermal growth factor concentrations were remarkably decreased by sialoadenectomy (Sx): 410 +/- 65 (SE) pg/ml (n = 10) in intact animals; and undetectable in Sx mice (n = 5). Plasma TGF alpha levels were 90 and 40 pg/ml in intact and in Sx animals, respectively. Ten million SHIN-3 cells inoculated into nu/nu mice formed tumors in 100% of mice, and tumors grew progressively. Implantabilities and tumor growth rates of inoculated cells were not affected by Sx and even by Sx and anti-mouse epidermal growth factor antibody treatment. However, anti-TGF alpha monoclonal antibody (mAb) administered to SHIN-3 cell-inoculated Sx animals drastically reduced the tumor growth. Although 10(7) SHIN-3 cells formed tumors in this group, tumor growth was significantly inhibited by 10 micrograms of anti-TGF alpha mAb given 3 times a week, and growth inhibitions were more by 20 micrograms of anti-TGF alpha mAb. Moreover, as aggressive tumor growth as that in Sx animals was resumed by the cessation of anti-TGF alpha mAb treatments. All these data suggested the biological importance of a TGF alpha/epidermal growth factor receptor autocrine mechanism on the growth of this cell line in vivo.

Animals↗
PubMed1991

Cardiovascular effects of E4080, a novel bradycardiac agent with coronary vasodilating properties, in anesthetized dogs.

The cardiohemodynamic effects of E4080, a novel bradycardiac agent with a coronary vasodilating feature, were studied in anesthetized open-chest dogs. E4080 (0.3 and 1 mg/kg i.v.) decreased heart rate (HR), mean aortic pressure (MAP) and total peripheral resistance, and increased coronary blood flow (CBF) without affecting cardiac output and the electrocardiogram. The maximum rate of rise in left ventricular pressure decreased at 1 mg/kg. In addition, E4080 (0.3 and 1 mg/kg i.v.) decreased myocardial oxygen consumption. On administration in sinus node artery, E4080 (10 and 30 micrograms) selectively decreased HR. Glibenclamide, an ATP-sensitive K+ channel blocker (5 mg/kg i.v.), inhibited both the increase in CBF and the decrease in MAP caused by E4080 (1 mg/kg i.v.) but did not inhibit the bradycardia. These results suggested that E4080 has both bradycardiac and coronary vasodilating effects, and that activation of ATP-sensitive K+ channel contributes to the vasodilating action of E4080 but not to the bradycardiac action.

Animals↗
PubMed1991

Site-directed mutants, at position 166, of RTEM-1 beta-lactamase that form a stable acyl-enzyme intermediate with penicillin.

Class A beta-lactamases are known to hydrolyze substrates through a Ser70-linked acyl-enzyme intermediate, although the detailed mechanism remains unknown. On the basis of the tertiary structure of the active site, the role of Glu166 of class A enzymes was investigated by replacing the residue in RTEM-1 beta-lactamase with Ala, Asp, Gln, or Asn. All the mutants, in contrast to the wild-type, accumulated a covalent complex with benzylpenicillin which corresponds to an acyl-enzyme intermediate. For the Asp mutant, the complex decayed slowly and the hydrolytic activity was slightly retained both in vivo and in vitro. In contrast, the other mutants lost the hydrolytic activity completely and their complexes were stable. These results indicate that the side-chain carboxylate of Glu166 acts as a special catalyst for deacylation. Residues for deacylation have not been identified in other acyl enzymes, such as serine proteases and class C beta-lactamases. Furthermore, the acyl-enzyme intermediates obtained are so stable that they are considered to be ideal materials for crystallographic studies for elucidating the catalytic mechanism in more detail. In addition, the mutants can more easily form inclusion bodies than the wild-type, when they are produced in a large amount, suggesting that the residue also plays an important role in proper folding of the enzyme.

Acylation↗
PubMed1991

Induction of putative new cytochrome P450 isozyme in rat liver by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Changes in hepatic enzymes responsible for mutagenic activation of food mutagens-carcinogens by treatment with 2-amino-1-methyl-6-phenylimidazo [4, 5-b]pyridine (PhIP) in male F344 rats were examined using the Salmonella mutation test, with 3 heterocyclic aromatic amines as substrates, and further characterized by Western blot analysis with anti-P450 monoclonal antibodies (MoAbs) against rat P450IA1 and P450IA2. Enzymatical and immunochemical analyses indicated that PhIP could induce a putative new P450 isozyme, mol. wt., 51,000, together with P450IA1 and P450IA2 in rat liver microsomes. The profiles of induced P450 molecular species varied dramatically, depending on the time after PhIP administration.

Animals↗
PubMed1991

Comparison of the effects of endothelin and Bay k 8644 on cardiohemodynamics in anesthetized pigs.

The effects of endothelin on cardiohemodynamics in anesthetized open-chest pigs were compared with those of the Ca2+ channel agonist Bay k 8644. I.v. administration of endothelin (0.1-1 microgram/kg) dose relatedly decreased coronary blood flow velocity (CFV), cardiac output, the maximal rate of rise in left ventricular pressure (LV dP/dtmax) and heart rate, and increased systolic and diastolic blood pressure and systemic vascular resistance. Bay k 8644 (0.1-30 micrograms/kg) showed similar effects on cardiohemodynamics, except that it caused a substantial increase in LV dP/dtmax and did not change stroke volume. I.c. administration of endothelin (0.1-1 microgram) into the left circumflex coronary artery (LCX) produced a dose-dependent and sustained decrease in CFV followed by a marked increase in the ST segment of epicardial electrocardiograms and a depression in myocardial shortening in the region supplied by LCX. An increase in left ventricular end-diastolic pressure and a reduction in LV dP/dtmax were also observed after endothelin. In contrast, Bay k 8644 caused a transient decrease in CFV and an increase in LV dP/dtmax, without causing any changes indicative of myocardial ischemia. Although the reduction in CFV after i.c. endothelin was not affected by i.v. infusion of nicardipine (1 microgram/kg per min), the reduction in CFV observed after i.c. Bay k 8644 was significantly suppressed (P less than 0.05). We conclude that endothelin is a more potent coronary vasoconstrictor than Bay k 8644 and provokes marked myocardial ischemia.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Antigen-independent T cell activation mediated by a very late activation antigen-like extracellular matrix receptor.

Cell-cell and cell-extracellular matrix (ECM) binding mediated by integrin molecules has been implicated in lymphocyte migration and adhesion. We describe here that ECM binding triggers antigen-independent activation of T cell functions. Fibronectin and vitronectin, when coated on plates, not only acted synergistically on anti-CD3-induced serine esterase release in a murine cytotoxic T lymphocyte clone and interleukin 2 production in a murine helper T cell hybridoma but also could trigger these responses alone. All these stimulatory effects of ECM were abrogated by a monoclonal antibody which reacts with a unique very late activation antigen-like integrin and this monoclonal antibody, when coated on plates, exhibited a similar synergistic effect to that of ECM proteins. Therefore, ECM receptors expressed on activated T cells appear to play an important role in triggering T cell effector functions in localized tissues abundant in ECM proteins.

Antigens, Differentiation, T-Lymphocyte↗