Biomedical subjects

Y Hirano

Publications and source records attributed to Y Hirano.

At least 73 records · Page 4Linked to original sources

PubMed2000

Impaired vasodilatation response to amrinone in the forearm of patients with congestive heart failure: role of endothelium-derived nitric oxide.

Recent in vitro experiments have shown that amrinone enhances the release of nitric oxide (NO) from the endothelium and induces NO mediated vasodilatation. This in vivo study examined whether amrinone causes vasodilatation mediated by endothelium-derived NO, and whether this effect is attenuated in patients with endothelial dysfunction. Eight patients with congestive heart failure and 10 age- and sex-matched healthy volunteers were studied. Forearm blood flow (FBF) was measured before and during infusion of drugs of acetylcholine, amrinone, and nitroglycerin in incremental doses. After the completion of these measurements, 100 micromol of N(G)-monomethyl-L-arginine (L-NMMA) was infused intraarterially. Thereafter, FBF measurement in response to incremental doses of amrinone was repeated. Infusion of incremental doses of amrinone caused a comparable increase in amrinone plasma concentration in both groups. Baseline FBF was 3.2+/-0.79 ml/min/100 ml in controls vs. 2.91+/-0.79 ml/min/100 ml in patients (p = 0.43). In both groups, FBF increased in response to acetylcholine, amrinone, and nitroglycerin. During infusion of the highest dose of nitroglycerin, FBF was not different between the two groups (p = 0.51); however, FBF during infusion of the highest doses of acetylcholine and amrinone was significantly less in patients than in controls: 9.75+/-2.69 vs. 24.87+/-8.65 ml/min/100 ml (p < 0.001) and 3.79+/-1.21 vs. 7.15+/-2.06 ml/min/100 ml (p < 0.001), respectively. L-NMMA significantly depressed the increase in FBF in response to amrinone in controls, but not in patients. In conclusion, the selective PDE III inhibitor, amrinone, has endothelium-derived NO-mediated vasodilating effects in addition to direct effects. This property may be impaired in patients with endothelial dysfunction.

Acetylcholine↗

PubMed2000

Effect of Am-80, a retinoid derivative, on 2, 4-dinitrofluorobenzene-induced contact dermatitis in mice.

Retinoids have many pharmacological activities, including anti-inflammatory action and antiangiogenesis, effected through the regulation of various gene transcriptions. In this study, we investigated the effect of Am-80, one of the retinoic acid derivatives, on hapten-induced contact hypersensitivity in BALB/c mice. After application of 2,4-dinitrofluorobenzene (DNFB) to the ears of the mice, severe contact hypersensitivity with marked infiltration of inflammatory cells and hypertrophy of the epidermis was caused. The thickness of the ears increased biphasically and reached a peak 3 and 24 h after the DNFB challenge. Am-80 significantly inhibited ear thickness in the late-(24 h), but not the early-phase (3 h) reaction in a dose-dependent manner. In a histopathological study, obvious depression of edema and infiltration of inflammatory cells was observed in the ears of mice treated with Am-80. Am-80 inhibited the levels of expression in mice ears of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6), but not tumor necrosis factor-alpha (TNF-alpha) or interleukin-4 (IL-4). Furthermore, Am-80 inhibited the antigen-induced production of some cytokines, including IFN-gamma and IL-6, but not IL-4, in vitro. Therefore, Am-80 inhibited hapten-induced contact hypersensitivity through the direct inhibition of inflammatory cytokines such as IFN-gamma and IL-6.

Animals↗

PubMed2000

Influence of gelatin complexation on cell proliferation activity and proteolytic resistance of basic fibroblast growth factor.

The objective of this study is to investigate the influence of gelatin complexation on the biological activity of basic fibroblast growth factor (bFGF) and its resistance to trypsin digestion. When bFGF was mixed at 37 degrees C with acidic gelatin with an isoelectric point (IEP) of 5.0, the activity to promote in vitro proliferation of BHK cells became lower compared with that of free bFGF, in contrast to mixing with the basic gelatin with an IEP of 9.0. A maximum reduction in the bFGF activity was observed for the bFGF-gelatin complex prepared at a mixing molar ratio of 1/1. The bFGF activity of cell proliferation reduced at the initial period after mixing with the acidic gelatin at 37 degrees C, followed by no substantial change. Complexation with the acidic gelatin at 4 degrees C had no influence on the bFGF activity, irrespective of the bFGF/gelatin ratio and complexation time. The biological activity of bFGF was reduced by the trypsin treatment, but the reduced extent was suppressed through gelatin complexation at 37 degrees C. In an electrophoresis study, the protective effect of gelatin complexation on the trypsin digestion was also confirmed in terms of the molecular weight loss. It is possible that the complexing gelatin covers bFGF molecules, resulting in suppression of their interaction with the cell surface receptor as well as protection from their enzymatic attack.

Animals↗

PubMed2000

YM-40461 improves airway clearance in guinea pigs with induced subacute bronchitis.

The effects of the surfactant secretagogue YM-40461 on the mucociliary transport (MCT) velocity were examined in guinea pigs with induced bronchitis. Guinea pigs were exposed to SO2 gas (900 ppm, 3 h/d) for 5 d. MCT velocity was measured by the movement of a 30% gelatin solution containing Evans blue dye placed on the tracheal mucosal surface. Repeated doses of YM-40461 improved the MCT guinea pigs with bronchitis within 5 d after the completion of SO2 exposure, with an ED50 value of 3.1 mg/kg p.o. At a dose of 10 mg/kg p.o., YM-40461 restored MCT to the control level (98.0% recovery). Ambroxol, bromhexine and salbutamol also improved MCT, but were far less effective than YM-40461. Airway fluid collected from bronchitic animals revealed increased disaturated phosphatidylcholine (DSPC, a major component of surfactants)-to-protein ratio and decreased surface tension produced by YM-40461 treatment (10 mg/kg). These results suggest that YM-40461 ameliorates MCT dysfunction in animals with SO2 gas-induced bronchitis by increasing the DSPC-to-protein ratio in the airway.

Animals↗

PubMed2000

YM-40461, a potent surfactant secretagogue, improves mucociliary clearance in SO2-exposed guinea pigs.

The effects of the new pulmonary surfactant secretagogue YM-40461, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl) urea, on tracheal mucociliary transport (MCT) were assessed using guinea pigs with acute bronchitis. Acute bronchitis was induced by SO2 gas exposure (400 ppm for 3 h). MCT velocity was measured by means of the dye gelatin technique. YM-40461 at doses of 1-10 mg/kg, p.o. induced recovery of MCT function, with an ED50 value of 2.4 mg/kg. Maximal recovery (78.0+/-12.5%) was observed 2 h in the animals treated with 10 mg/kg of YM-40461. Ambroxol and bromhexine showed less effect on the MCT dysfunction than YM-40461. An artificial surfactant (Surfacten) also aided recovery. YM-40461 at a dose of 10 mg/kg, p.o. significantly improved surfactant production without affecting mucus secretion. These results show that YM-40461 ameliorates MCT dysfunction caused by SO2 exposure by activation of pulmonary surfactant secretion.

Animals↗

PubMed2000

Inhibitory effect of lactoferrin on the adhesion of Prevotella nigrescens ATCC 25261 to hydroxyapatite.

Prevotella nigrescens ATCC 25261 (P. nigrescens) cells adhere well to hydroxyapatite treated with citrate (CHA), but the attachment is drastically inhibited by lactoferrin (LF). To determine the nature of the iron-free LF responsible for inhibiting P. nigrescens cell attachment, this study tested the duration and frequency of LF treatment of CHA and the effects of divalent and trivalent ferric ions. The inhibitory effect on the attachment of P. nigrescens was somewhat higher with bovine LF than human LF. Apo LF effectively inhibited P. nigrescens cell attachment to CHA, and almost abolished attachment at a concentration of 0.4 mg/ml. Fe3+ saturated LF was unable to inhibit attachment, whereas Fe2+ showed a slight effect under the same conditions. The LF absorbed rapidly to CHA in less than 10 min. With a lower concentration (0.1 mg/ml) of LF, only three treatments of CHA were required for the maximum inhibition of P. nigrescens cell attachment. The quantity of LF adsorbed to the hydroxyapatite (HA) and to P. nigrescens cells was determined by use of [3H]-LF. Approximately 25 micrograms of LF protein adsorbed to 5 mg of HA at saturation, and approximately 0.25 microgram of LF did so to the 6 x 10(8) cells.

Adsorption↗

PubMed2000

[Relationship between endothelial function and female hormone level in very old females: evaluation from ischemic reactive hyperemic response in forearm vessels].

Recently, the mechanism of longevity in females was proposed to be associated with female hormones. This study examined the effect of aging and sex on vascular endothelial function, and the relationship between female hormone level and endothelial function by ischemic reactive hyperemic response in the forearm using plethysmography. The study population consisted of 246 healthy subjects aged from 20 to 76 years (119 males, 127 females) and 20 healthy females aged 85 years and older (85 to 103 years; mean age 94 years) without distinct cardiovascular disease, hypertension, diabetes mellitus, renal disease, liver dysfunction or anemia. Levels of the female hormones, estradiol and estriol, were measured in females aged more than 85 years. The duration of reactive hyperemia decreased with aging, but the difference between males and females was not significant at any age. In females, the duration was markedly decreased from 110 +/- 36 sec in the fifties to 81 +/- 29 sec in the sixties or older (p < 0.05). Excess flow also showed similar changes to the duration of reactive hyperemia. The duration of reactive hyperemia and excess flow in females aged 85 years and older were similar to those in the fifties, but was significantly longer than those in females 60 years or older. The concentrations of estradiol (44.9 +/- 27.1 pg/ml) and estriol (22.1 +/- 13.4 pg/ml) in females aged 85 years were higher than in the sixties. There was a positive correlation between the duration of reactive hyperemia and the concentration of estradiol (r = 0.56, p < 0.01) or estriol (r = 0.57, p < 0.01). In summary, vascular endothelial function was impaired gradually with aging, but preservation of the function in healthy, very old females was closely associated with levels of female hormone.

Adult↗

PubMed2000

[Penile metastasis from renal cell carcinoma: a case report].

Penile metastasis is rare. It occurs in the advanced stage of genitourinary cancer, with many other metastases in various organs. All 7 patients with penile metastasis of renal cell cancer, reported in the Japanese literature, died within a year. Our case was not the exception. A 69-year-old male presented with right flank pain and penile induration. Right renal cancer with liver invasion and multiple pulmonary metastases were found. Microscopic examination revealed a sarcomatous pattern. He died 4 months later.

Aged↗

PubMed2000

[Carotid endarterectomy: how we do it].

Carotid endarterectomy (CEA) clearly benefits high stroke-risk patients with coronary or peripheral vascular disease, but its value of procedures is not still recognized for thoracic surgeons in Japan. Therefore we reviewed our technique of CEA and presented its usefulness and necessity.

Carotid Arteries↗

PubMed2000

[Burned-out testicular tumor: a case report].

A 29-year-old man was referred to our hospital with loss of appetite and a left lower abdominal mass. A small nodule was palpable in his left testis and ultrasonographic examination demonstrated that the nodule was low echoic. Computed tomography showed a large mass in his left retroperitoneal space. We thought the mass was a metastatic lesion from a testicular tumor. Left orchiectomy was done and microscopic examination revealed no viable tumor cells. Only fibrous tissue, small calcified areas, and hyaline bodies were found. As tumor markers were normalized after 3 courses of chemotherapy with bleomycin, etoposide, and cisplatine, the retroperitoneal mass was removed with the left kidney. It consisted of embryonal carcinoma, mature teratoma, and yolk sac tumor. One course of adjuvant chemotherapy was done and the patient has since been free from recurrence. We suppose that the tumor was a so-called 'burned-out' testicular tumor.

Adult↗

PubMed1999

Multicenter study of paroxysmal dyskinesias in Japan--clinical and pedigree analysis.

To investigate the clinical features of paroxysmal dyskinesias and carry out a pedigree analysis, we conducted a multicenter survey in Japan. A questionnaire was mailed to 229 medical institutions. A total of 150 patients with paroxysmal kinesigenic choreoathetosis (PKC), including 53 sporadic cases and 97 affected individuals from 32 pedigrees, were identified. The mean age of onset of PKC was 8.8 years, and 80% of the cases were men. Of the 32 pedigrees with familial occurrence, 18 (56%) were compatible with an autosomal-dominant inheritance (AD) with complete penetrance, and seven (22%) had AD with incomplete penetrance; the remaining seven were sibling recurrence cases with apparently healthy parents. In six of seven familial cases with incomplete penetrance, the disease gene was thought to be transmitted by clinically unaffected females. Paroxysmal dystonic choreoathetosis (PDC) was found in five cases, including two sporadic cases and three affected individuals from two pedigrees; the mean age of onset was 0.6 years, and a male predominance was noted (male:female = 4:1). There was one case of paroxysmal hypnogenic dyskinesia and one case of paroxysmal exertion-induced dyskinesia. There is an unexplained male predominance for paroxysmal dyskinesias. When the genetic defect of patients with paroxysmal dyskinesias is identified, the pathophysiology of the disease will become more clear.

Adolescent↗

PubMed1999

A new, simple method for measuring mucociliary clearance in guinea-pigs.

Airway mucociliary transport (MCT), which continuously removes inhaled particles and cellular debris from deep in the lung, is impaired in a number of diseases such as bronchitis and asthma. In order to determine the effects of candidate drugs on MCT function in the airway, a new in situ method to measure MCT function was established. MCT function is represented by the distance a gelatin solution containing Evans blue as a marker moves after injection into the trachea. The basal rate of dye transport in non-treated guinea-pigs was 4.4+/-0.2 mm/min. The beta2-adrenoceptor agonist salbutamol (2, 6, 10, 20 mg/kg, po), dose-dependently accelerated the basal MCT rate. However, its effect was completely inhibited by pretreatment with the non-selective beta -adrenoceptor antagonist, propranolol (1 mg/kg, iv). MCT function in guinea-pigs was significantly attenuated to 2.6+/-0.3 mm/min by SO2 gas exposure. Salbutamol failed to prevent MCT dysfunction in SO2-exposed animals at doses previously shown to accelerate basal MCT rate. This simple method is useful for estimating MCT function in several airway disease models and for examining new drugs designed to improve MCT function in airway diseases.

Adrenergic beta-Antagonists↗

PubMed1999

Clinical application of an in vitro chemosensitivity test, the Histoculture Drug Response Assay, to urological cancers: wide distribution of inhibition rates in bladder cancer and renal cell cancer.

To investigate the variations in chemosensitivity of individual cancers, we performed an in vitro chemosensitivity test, the Histoculture Drug Response Assay (HDRA), on fresh biopsied or surgical specimens. They were 26 bladder cancers and 19 renal cell cancers. Ten anticancer drugs were tested. By prolonging the drug exposure time to 7 days, we obtained reliable results. The mean inhibition rates (IRs) were higher for bladder cancer than for renal cell cancer, and the difference was significant for cisplatin, carboplatin, vinblastine, mitomycin C, and adriamycin. There was no significant correlation between the histological grade of the tumor and HDRA sensitivity. IR values showed a wide distribution and cancers could be classified into two groups of sensitive and resistant. This was especially true for 4-hydroxy-ifosfamide. Three bladder cancer patients with evaluable lesions were treated with drugs selected on the basis of the results of the HDRA. One patient achieved a complete response and the other patients showed a partial response. Our results suggest that chemosensitivity is independent of the clinicopathological classification of cancer, and that the HDRA may be useful for selecting the effective anticancer drug for patients with urological cancer.

Antineoplastic Agents↗

PubMed1999

The change of bone mineral density in secondary osteoporosis and vertebral fracture incidence.

Causes of secondary osteoporosis are diverse, and bone changes in this condition have been elucidated less than those in primary osteoporosis. In this study, bone mineral density (BMD) was measured in the lumbar spine, distal and proximal sites of the radius, and calcaneus in representative disorders that cause secondary osteoporosis to evaluate its changes. Also, the incidence of nontraumatic vertebral fracture was examined. The subjects were 80 patients with rheumatoid arthritis, 50 patients undergoing glucocorticoid (steroid) therapy, 20 patients with chronic hepatitis, 24 patients with liver cirrhosis, 14 patients with primary biliary cirrhosis (PBC), 26 patients with diabetes mellitus, and 20 postgastrectomy patients; all were ambulatory female outpatients. Two hundred females with primary osteoporosis were examined as a control group. The reproducibility of the measurement of the BMD was satisfactory at about 3% by all methods of measurement employed. Concerning changes in BMD, periarticular trabecular bone density was most markedly reduced in the rheumatoid arthritis group. The patients receiving steroid therapy showed the greatest decreases in the trabecular bone mineral density at the distal 4% of the radius and lumbar spinal BMD. In addition, the threshold of vertebral fracture was higher in those undergoing steroid therapy than in those with primary osteoporosis. The patients with PBC showed the greatest decreases in BMD among patients with chronic liver disorders, and no decrease in BMD was noted in the chronic hepatitis group. BMD was reduced only in the radius in the patients with diabetic mellitus, and it was generally reduced in the postgastrectomy patients. BMD of the calcaneus was not reduced in any group.

Adrenal Cortex Hormones↗

PubMed1999

Voltage-shift of the current activation in HERG S4 mutation (R534C) in LQT2.

OBJECTIVE: Recently, a novel missense mutation (R534C) in the S4 region of human ether-a-go-go-related gene (HERG) was identified in one Japanese LQT2 family. The S4 region presumably functions as a voltage sensor. However, it has not yet been addressed whether the S4 region of HERG indeed functions as a voltage sensor, and whether these residues play any role in abnormal channel function in cardiac repolarization. METHODS: We characterized the electrophysiological properties of the R534C mutation using the heterologous expression system in Xenopus oocytes. Whole cell currents were recorded in oocytes injected with wild-type cRNA, R534C cRNA, or a combination of both. RESULTS: Clinical features--QTc intervals of all affected patients with R534C mutation in HERG are prolonged ranging from 460 to 680 ms (averaged QTc interval > 540 ms). One member of this family had experienced sudden cardiac arrest, and other suffered from recurrent palpitation. Electrophysiology--Oocytes injected with R534C cRNA did express functional channels with altered channel gating. Kinetic analyses revealed that the R534C mutation shifted the voltage-dependence of HERG channel activation to a negative direction, accelerated activation and deactivation time course, and reduced steady-state inactivation. Quantitative analyses revealed that this mutation did not cause apparent dominant-negative suppression. Computer simulation--Incorporating the kinetic alterations of R534C, however, did not reproduce prolonged action potential duration (APD). CONCLUSIONS: The data revealed that arginine at position 534 in the S4 region of HERG is indeed involved in voltage-dependence of channel activation as a voltage sensor. Our examination indicated that HERG current suppression in R534C mutation was the least severe among other mutations that have been electrophysiologically examined, while affected patients did show significant QT prolongation. This suggest that another unidentified factor(s) that prolong APD might be present.

Action Potentials↗

PubMed1999

Potentiation of recombinant L-type Ca channel currents by alpha1-adrenoceptors coexpressed in baby hamster kidney (BHK) cells.

In cardiac myocytes, the effect of alpha1-adrenergic stimulation on L-type Ca current remains to be clarified. We examined this issue by the transient coexpression of alpha1-adrenoceptors on BHKC12 cells, where recombinant Ca channels composed of cardiac alpha1 subunit and skeletal beta, gamma, alpha2/delta subunits were stably expressed. After transfection of plasmid DNA encoding bovine alpha1C-adrenoceptors, bath-applied phenylephrine potentiated the cloned Ca channel current during perforated-patch whole-cell recording by 26+/-6% in 6 out of 12 cells. The potentiation was elicited also by methoxamine, and was blocked by prazosin. Phenylephrine also increased the channel open probability during cell-attached single channel recording in 7 out of 15 cells. The ratio of successful modulation of Ca channels was in accordance with the ratio of successful expression of alpha1-adrenoceptors, as estimated by beta-galactosidase staining. These results suggest that the stimulation of alpha1C-adrenoceptors is linked to potentiation of cardiac L-type Ca current. BHK cells provide a valuable expression system to study the modulation of Ca channels evoked by a receptor stimulation.

Animals↗

PubMed1999

Preparation of poly(ethylene glycol)-polystyrene block copolymers using photochemistry of dithiocarbamate as a reduced cell-adhesive coating material.

This article reports a novel preparation method of poly(ethylene glycol) (PEG)-polystyrene (PST) amphiphilic block copolymers with well-defined block lengths by using photopolymerization of an iniferter, benzyl N,N-diethyldithiocarbamate. PEG macroiniferters, which were prepared by end-capping of PEG monomethyl ethers with benzyl N,N-diethyldithiocarbamate group at one end, were irradiated with UV light in the presence of styrene (ST). NMR analyses showed that the PST block was chain-extended from the PEG block, resulting in the preparation of PEG-PST block copolymers. The number-average molecular weights of the copolymers increased almost linearly with irradiation time, light intensity, and concentration of ST. The polydispersities of the copolymers remained relatively small throughout the reaction (Mw/Mn approximately 1.3). The composition of two PEG-PST block copolymers thus obtained was as follows: PEG (Mn; 1.9 x 10(3) gmol(-1))-PST (3.0 x 10(3) gmol(-1)) and PEG (4.9 x 10(3) gmol(-1))-PST (2.6 x 10(3) gmol(-1)). These copolymers were coated onto a poly(ethylene terephthalate) film surface. X-ray photoelectron spectroscopy analyses and water wettability measurements showed that the PST block was enriched at the outermost layer as cast in air, whereas upon immersion into water, the PEG block was oriented toward water. Enhanced wettability was observed for the diblock copolymer with a higher PEG content. Significantly reduced cell adhesion was observed on both the coated surfaces. Thus, the PEG-PST block copolymer may function as a cell adhesion-resistant coating which reduced cell-substrate interaction.

Animals↗

PubMed1999

Fibroma of tendon sheath arising from the radio-ulnar joint.

A report of a 65-year-old male with a tumor arising from synovial tissue of the radio-ulnar joint. On magnetic resonance imaging, the tumor was demonstrated as a heterogeneous and lobulated mass with a low signal intensity both in T1- and T2-weighted images. Histological findings of the tumor were identical to those of fibroma of the tendon sheath. In the peripheral villous synovial tissue, several small and fibrous nodules were observed, and their histological features were identical to those of the main tumor. Immunohistochemically, the tumor cells showed diffuse and intense reactivity to vimentin, muscle actin and S-100. These results indicated that the tumor might be a fibromatous analog of synovial chondromatosis.

Actins↗