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M Yoshida

Publications and source records attributed to M Yoshida.

At least 433 records · Page 24Linked to original sources

Role of potassium channels in catecholamine secretion in the rat adrenal gland.

We elucidated the functional contribution of K(+) channels to cholinergic control of catecholamine secretion in the perfused rat adrenal gland. The small-conductance Ca(2+)-activated K(+) (SK(Ca))-channel blocker apamin (10-100 nM) enhanced the transmural electrical stimulation (ES; 1-10 Hz)- and 1, 1-dimethyl-4-phenyl-piperazinium (DMPP; 5-40 microM)-induced increases in norepinephrine (NE) output, whereas it did not affect the epinephrine (Epi) responses. Apamin enhanced the catecholamine responses induced by acetylcholine (6-200 microM) and methacholine (10-300 microM). The putative large-conductance Ca(2+)-activated K(+) channel blocker charybdotoxin (10-100 nM) enhanced the catecholamine responses induced by ES, but not the responses induced by cholinergic agonists. Neither the K(A) channel blocker mast cell degranulating peptide (100-1000 nM) nor the K(V) channel blocker margatoxin (10-100 nM) affected the catecholamine responses. These results suggest that SK(Ca) channels play an inhibitory role in adrenal catecholamine secretion mediated by muscarinic receptors and also in the nicotinic receptor-mediated secretion of NE, but not of Epi. Charybdotoxin-sensitive Ca(2+)-activated K(+) channels may control the secretion at the presynaptic site.

Acetylcholine↗

Interaction of SK(Ca) channels and L-type Ca(2+) channels in catecholamine secretion in the rat adrenal gland.

We elucidated the interaction of small-conductance Ca(2+)-activated K(+) (SK(Ca)) channels and L-type Ca(2+) channels in muscarinic receptor-mediated control of catecholamine secretion in the isolated perfused rat adrenal gland. The muscarinic agonist methacholine (10-300 microM) produced concentration-dependent increases in adrenal output of epinephrine and norepinephrine. The SK(Ca) channel blocker apamin (1 microM) enhanced the methacholine-induced catecholamine responses. The facilitatory effect of apamin on the methacholine-induced catecholamine responses was not observed during treatment with the L-type Ca(2+) channel blocker nifedipine (3 microM) or Ca(2+)-free solution. Nifedipine did not affect the methacholine-induced catecholamine responses, but it inhibited the responses during treatment with apamin. The L-type Ca(2+) channel activator Bay k 8644 (1 microM) enhanced the methacholine-induced catecholamine responses, whereas the enhancement of the methacholine-induced epinephrine and norepinephrine responses were prevented and attenuated by apamin, respectively. These results suggest that SK(Ca) channels are activated by muscarinic receptor stimulation, which inhibits the opening of L-type Ca(2+) channels and thereby attenuates adrenal catecholamine secretion.

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

Structure of the middle ear and auditory tube in the house musk shrew, Suncus murinus.

Anatomical features of the middle ear and auditory tube (AT) in the house musk shrew, Suncus murinus, were examined by dissection and light microscopy. The tensor veli palatini (TVP) and tensor tympani (TT) have no connections with the wall or cartilage of the AT although they are connected by the intermediate tendon. None of the levator veli palatini (LVP) muscle bundles are attached to the AT. The salpingopharyngeus (SA) alone has its origin on the caudal edge of the tubal cartilage. The origin extends to the pharyngeal two thirds of the cartilage. The SA originates perpendicular to the AT and runs caudomedialward. Some SA muscle bundles intermingle with those of the palatopharyngeus to end on the dorsal wall of the pharynx. The observations provide no evidence that the TVP, LVP and TT have any role in AT function. The only muscle affecting the AT function in S. murinus is the SA, and it would be the AT dilator.

Animals↗

Detection of Herpes simplex virus DNA in non-herpetic areas of patients with eczema herpeticum.

BACKGROUND: Patients with atopic dermatitis may develop a widespread cutaneous herpes simplex virus (HSV) infection called eczema herpeticum. OBJECTIVE: We examined the possible routes of indirect HSV dissemination in 10 patients with eczema herpeticum, although direct spread of HSV is the most likely route of infection. METHODS: Specimens were collected from hands and 'non-herpetic' areas (i.e. without eczema herpeticum), with or without eczematous and/or erythematous lesions of atopic dermatitis, of 10 patients with eczema herpeticum. We tried to detect HSV DNA in the samples by polymerase chain reaction. RESULTS: HSV DNA was frequently detected on both hands and on cutaneous surfaces clinically free of eczema herpeticum. These patients had scratched such lesions because of itching. Moreover, they had taken baths the day before the examination. CONCLUSION: These results suggest that there may be two routes of indirect transmission of this virus, namely via manual scratching of herpetic lesions or via a contaminated bath towel or item of underwear.

Adolescent↗

Once-daily theophylline reduces serum eosinophil cationic protein and eosinophil levels in induced sputum of asthmatics.

BACKGROUND: Because eosinophilic airway inflammation is a characteristic feature of bronchial asthma, the treatment of airway inflammation is important in the management of asthma. Theophylline has been reported to reduce airway inflammation, in addition to its well-known bronchodilating effect. OBJECTIVE: In order to evaluate the effects of theophylline on airway inflammation, we investigated 48 subjects with mild and moderate asthma. METHODS: The patients were randomly divided into two groups, with or without theophylline treatment (control n = 24; theophylline, n = 24). We examined the level of serum eosinophil cationic protein (ECP), induced sputum samples, and peak expiratory flow (PEF) and obtained spirograms before and after 4 weeks of treatment with once-daily theophylline (200-600 mg/day) of subjects with mild or moderate asthma. RESULTS: Theophylline significantly increased morning and evening PEF and significantly decreased the diurnal variation of PEF. After treatment with theophylline, both serum ECP and the percentage of eosinophils in induced sputum were significantly decreased. In contrast, peripheral blood eosinophil count was unchanged after treatment with theophylline. CONCLUSIONS: These findings suggest that theophylline reduces airway inflammation and the severity of asthma, presumably via suppression of both eosinophil activity and subsequent eosinophil infiltration of the airways.

Adolescent↗

Close association between high serum ALT and more rapid recurrence of hepatocellular carcinoma in hepatectomized patients with HCV-associated liver cirrhosis and hepatocellular carcinoma.

We investigated whether or not a high serum alanine aminotransferase (ALT) level is associated with a more rapid recurrence of hepatocellular carcinoma (HCC) in hepatectomized patients with hepatitis C virus (HCV)-associated liver cirrhosis (LC) (HCV-LC) and HCC. Thirty-three hepatectomized patients with HCV-LC and HCC of a single nodule who had no histologic evidence of portal or hepatic vein invasion and who had been followed up for more than 3 years were included in the study. They were subdivided into two groups according to their serum ALT levels, ALT being a well-known marker of inflammatory necrosis in the liver. Seventeen patients whose serum ALT levels showed several peaks or plateaus above 80 international units (IU) were designated as the high ALT group, and 16 patients whose serum ALT levels showed a sustained low level below 80 IU until the first recurrence were designated as the low ALT group, and the interval between hepatectomy and the first recurrence was observed. In the high ALT group, HCC recurred within 3 years in 70.6% of the patients. In contrast, it recurred in only 18.8% of the low ALT group within the same period (p < 0.05). There was a significant difference (p = 0.0201) between the two groups in the cumulative nonrecurrence rate. The mean interval in recurrent patients between hepatectomy and the first recurrence in the high ALT group (23.6 +/- 2.8 months; mean +/- SE) was significantly (p < 0.02) shorter than that in the low ALT group (49.3 +/- 9.7 months). The expected interval between hepatectomy and recurrence was as short as 2.8 +/- 0.5 years (mean +/- SE) in the high ALT group, compared with 5.8 +/- 0.7 years in the low ALT group (p < 0.05). These results showed that the recurrence of HCC was accelerated in the high ALT group, suggesting that suppression of the rise in ALT level after hepatectomy by treatment with anti-inflammatory drugs may prolong the interval until recurrence by about 2 years in hepatectomized patients with HCC and HCV-LC.

Aged↗

Significance of carbohydrate antigen sialyl-Lewis X, sialyl-Lewis A, and possible unknown ligands to adhesion of human urothelial cancer cells to activated endothelium.

OBJECTIVE: To assess the contribution of the carbohydrate antigens, sialyl-Lewis X (sLe(x)) and sialyl-Lewis A (sLe(a)), which are known to be ligands for E-selectin, to the adhesion between human urothelial cancer cells and cytokine-activated human endothelial cells. MATERIALS AND METHODS: We studied the expression of sLe(x) and sLe(a) antigens of three bladder cancer cell lines (JTC 30, JTC 32, and T24) by flow cytometry and the adherence to interleukin 1beta-activated human umbilical vein endothelial cells (HUVEC). RESULTS: JTC 30 and JTC 32 cells expressed both sLe(x) and sLe(a) antigens, and showed adhesion to activated HUVEC, which was completely abolished by anti-E-selectin antibody. T24 cells expressed neither sLe(x) nor sLe(a) antigen, and did not adhere to activated HUVEC. Each of anti-sLe(a) or anti-sLe(x) antibody partially blocked the attachment of JTC 30 cells to activated HUVEC, and combination of these antibodies almost completely blocked the adhesion. The combination of antibodies did not significantly influence the adhesion of JTC 32 cells. CONCLUSION: These results indicate that both sLe(a) and sLe(x) carbohydrate antigens are involved in E-selectin-mediated adhesion of some urothelial cancers, and that there might be unknown ligands for E-selectin on urothelial cancer cells.

Antigens, Tumor-Associated, Carbohydrate↗

Meniscal tearing after ACL reconstruction.

The knees of 72 patients with unilateral anterior-cruciate- ligament (ACL) injury were analyzed before ACL reconstruction as well as by follow-up arthroscopy on the day of staple removal. At ACL reconstruction 31 lateral menisci and 40 medial menisci were found to be normal. 28 lateral menisci and 24 medial menisci were treated surgically, while 13 lateral menisci and 8 medial menisci with small or incomplete meniscal tearing were not treated. At follow-up arthroscopy there were 3 new cases of lateral meniscal tearing and 3 new cases of medial meniscal tearing in the groups diagnosed as normal prior to surgery. Two of the 13 cases with small or incomplete lateral meniscal tearing required resection, 8 healed and the other 3 demonstrated no progressive change. Four of the 8 cases with small or incomplete medial meniscal tears healed, 3 exhibited no progressive change and one required surgical treatment. There was no correlation between meniscal tearing and knee instability as indicated by a positive Lachman test or a positive pivot shift sign. The results of the present study indicate that ACL reconstruction prevents progressive changes in meniscal tears and will prevent secondary osteoarthritis, and that some small tears of the lateral meniscus require no surgical treatment.

Journal Article↗

Antidiabetic sulfonylurea enhances secretagogue-induced adrenocorticotropin secretion and proopiomelanocortin gene expression in vitro.

The presence of high-affinity binding sites for antidiabetic sulfonylureas (SUs) and the expression of SU receptor (SUR) messenger RNA in the adenohypophyseal cells have recently been reported. In this study, we examined the effects of SU on POMC gene expression and ACTH secretion using the AtT20PL cell line, a subclone of AtT20 in which the rat POMC 5'-promoter-luciferase fusion gene was stably incorporated. A representative SU glibenclamide inhibited the basal POMC 5'-promoter activity. In contrast, glibenclamide enhanced forskolin- or CRH-induced POMC expression in a dose-dependent manner. Interestingly, the latter effect was not observed under treatment with 3-isobutyl-1-methylxanthine, a nonselective phosphodiesterase inhibitor. Furthermore, diazoxide, an opener of the ATP-sensitive K+ channel, only antagonized the suppressive effect of glibenclamide. Lastly, RT-PCR analysis showed that mouse SUR (but not SUR2) messenger RNA was expressed in this cell line. These results suggest that, in AtT20PL cells, SU has dual effects, i.e. a suppressive effect on basal POMC expression through diazoxide-sensitive (ATP-sensitive) K+-channel-mediated mechanism, and an enhancing effect on cAMP/protein kinase A-stimulated POMC expression through a different mechanism (probably mediated by phosphodiesterase). To our knowledge, this is the first report showing the effect of SU on the expression of the anterior pituitary hormone gene.

8-Bromo Cyclic Adenosine Monophosphate↗

Developmentally regulated activity of CRM1/XPO1 during early Xenopus embryogenesis.

In this work, we have investigated the role of CRM1/XPO1, a protein involved in specific export of proteins and RNA from the nucleus, in early Xenopus embryogenesis. The cloning of the Xenopus laevis CRM1, XCRM1, revealed remarkable conservation of the protein during evolution (96.7% amino acid identity between Xenopus and human). The protein and mRNA are maternally expressed and are present during early embryogenesis. However, our data show that the activity of the protein is developmentally regulated. Embryonic development is insensitive to leptomycin B, a specific inhibitor of CRM1, until the neurula stage. Moreover, the nuclear localization of CRM1 changes concomitantly with the appearance of the leptomycin B sensitivity. These data suggest that CRM1, present initially in an inactive form, becomes functional before the initiation of the neurula stage during gastrula-neurula transition, a period known to correspond to a critical transition in the pattern of gene expression. Finally, we confirmed the gastrula-neurula transition-dependent activation of CRM1 by pull-down experiments as well as by the study of the intracellular localization of a green fluorescent protein tagged with a nuclear export signal motif during early development. This work showed that the regulated activity of CRM1 controls specific transitions during normal development and thus might be a key regulator of early embryogenesis.

Amino Acid Sequence↗

Rotation of F(1)-ATPase and the hinge residues of the beta subunit.

Rotation of a motor protein, F(1)-ATPase, was demonstrated using a unique single-molecule observation system. This paper reviews what has been clarified by this system and then focuses on the role of residues at the hinge region of the beta subunit. We have visualised rotation of a single molecule of F(1)-ATPase by attaching a fluorescent actin filament to the top of the beta subunit in the immobilised F(1)-ATPase, thus settling a major controversy regarding the rotary catalysis. The rotation of the beta subunit was exclusively in one direction, as could be predicted by the crystal structure of bovine heart F(1)-ATPase. Rotation at low ATP concentrations revealed that one revolution consists of three 120 degrees steps, each fuelled by the binding of an ATP to the beta subunit. The mean work done by a 120 degrees step was approximately 80 pN nm, a value close to the free energy liberated by hydrolysis of one ATP molecule, implying nearly 100% efficiency of energy conversion. The torque is probably generated by the beta subunit, which undergoes large opening-closing domain motion upon binding of AT(D)P. We identified three hinge residues, betaHis179, betaGly180 and betaGly181, whose peptide bond dihedral angles are drastically changed during domain motion. Simultaneous substitution of these residues with alanine resulted in nearly complete loss (99%) of ATPase activity. Single or double substitution of the two Gly residues did not abolish the ATPase activity. However, reflecting the shift of the equilibrium between the open and closed forms of the beta subunit, single substitution caused changes in the propensity to generate the kinetically trapped Mg-ADP inhibited form: Gly180Ala enhanced the propensity and Gly181Ala abolished the propensity. In spite of these changes, the mean rotational torque was not changed significantly for any of the mutants.

Adenosine Triphosphate↗

Preparation of griseofulvin for topical application using N-methyl-2-pyrrolidone.

We attempted to prepare a new griseofulvin formulation for topical application using N-methyl-2-pyrrolidone (NMP). Griseofulvin dissolves poorly in both water and oil, but dissolves in NMP to a concentration of about 100 mg/ml. A soybean oil-water emulsion with soybean lecithin and NMP as emulsifier and co-solvent, respectively, was prepared using a Microfluidizer, a high-pressure homogenizer. The size of the droplets in emulsion was about 200 nm, and the emulsion was stable for over 3 months. The skin permeation of griseofulvin through Yucatan micropig skin was studied in vitro using vertical type cells under donor phase open conditions. The permeation of griseofulvin from the NMP-water mixture (0-40%) into the skin tended to increase with increasing NMP concentration, although this finding was not statistically significant. Permeation from emulsion (oil phase, 20%; NMP 10-40%) was significantly higher than that from the water-NMP mixture. Permeation from the oil-NMP mixture was highest among the formulations investigated, and permeation from emulsion under donor phase closed conditions was significantly lower than that under open conditions. We believe that the evaporation of water from the emulsion after application to the skin was an important factor in skin permeation enhancement. When the emulsion containing 3% l-menthol was applied, a sufficient skin concentration (47 microg/cm3 in dermis) was obtained.

Administration, Topical↗

Participation of angiotensin II in pressor response and norepinephrine release to spinal nerve stimulation in pithed rats.

Experiments were carried out to examine whether endogenous angiotensin II (A-II) is involved in the regulation of release of norepinephrine (NE) elicited by the stimulation of spinal sympathetic nerves in pithed rats. It was assessed in terms of the alterations in concentrations of arterial blood plasma A-II and NE elicited by nerve stimulation (5 Hz, 50 V, 1 msec for 45 s) in pithed rats under vehicle or captopril (3 mg/kg, i.v.) treatment. Comparative study with pentobarbital anesthetized rats showed that pithing rats have the characteristics of lower basal blood pressure and lower NE level, whereas they have higher basal A-II level. In pithed rats treated with vehicle, pressor response to nerve stimulation was accompanied by increases in both A-II and NE level. In rats treated with captopril, the nerve stimulation caused about 40% lower increases in pressor response and NE level than those observed in rats treated with vehicle. These results suggest that the sympathetic nerve-induced NE release is facilitated by endogenous A-II in pithed rats, and that captopril exerts its inhibitory effect on the pressor response to nerve stimulation through the suppression of this interaction.

Angiotensin II↗

Effects of application voltage and cathode and anode positions at electroporation on the in vitro permeation of benzoic acid through hairless rat skin.

The enhancing effect of electroporation on the in vitro skin permeation of benzoate was evaluated. Needle and ring electrodes made of Ag/AgCl were connected to an electrical power source, which produced exponentially decaying pulses. The needle electrode was kept in contact with the skin surface, and the ring electrode was positioned either on or under the skin. The electrical pulse was applied to abdominal hairless rat skin at 150-600 V every minute from 4 to 6 h during the 10-h permeation experiment. Skin permeation of benzoate was promoted by electroporation and the effect was increased by application of a higher voltage. No immediate recovery to the control flux, however, was observed for high voltage groups after turning off the voltage application. When the cathode and anode were separated by the skin membrane by setting in the epidermal and dermal sides, respectively, an iontophoretic effect may also play a role in benzoate flux. These results indicated that the drug permeation by electroporation is the result of passive diffusion and an iontophoretic effect as well as the electroporation effect.

Animals↗

Quantitative evaluation of the bitterness of commercial medicines using a taste sensor.

The bitterness of 11 commercial medicines was evaluated both by a multichannel taste sensor and in human gustatory sensation tests with 15 volunteers. For basic drugs with amino groups in the molecule, such as quinine, there was a comparatively strong relative response electric potential (mV) of channels 1 or 2, those containing negatively charged membranes and the bitterness determined by human gustatory sensation tests. The suppression of the bitterness of quinine by sucrose and aspartame could be quantified using the artificial taste sensor and the results concurred with those from gustatory sensation tests. The usefulness of the sensor was thus confirmed for this type of compound. Anionic drugs, such as diclofenac sodium or salicylic acid gave rise in a negative response electric potential in channels 5 or 6, those containing positively charged membrane, seemed to be useful information even though their tastes are being sour rather than bitter. For drugs with both an amino (cationic) group and carboxylic acid (anionic) group in the molecule, such as theophylline, caffeine, and metronidazole, the relative response electric potential (mV) of channels containing negatively charged membranes was not increased, even though bitterness was observed in human gustatory sensation tests. Therefore, a different design of membrane component is required for more general evaluation of the bitterness of various medicines.

Aspartame↗

Resuscitation from fulminant myocarditis associated with refractory ventricular fibrillation.

Resuscitation was possible in a case of fulminant myocarditis with refractory ventricular fibrillation (Vf) using a percutaneous cardiopulmonary support system (PCPS). A 46-year old Japanese man suddenly experienced cardiopulmonary dysfunction shortly after the onset of flu symptoms, was promptly diagnosed as having fulminant myocarditis and PCPS was immediately initiated. On the second day in the hospital, refractory Vf occurred, which lasted for approximately 2h despite repeated efforts to terminate it. Finally, a large dose of steroids was administered. From the third day of hospitalization and onwards, the Vf disappeared totally. The patient completely recovered from such a serious state in 6 months. During the following 3 years, he has had no clinical symptoms of worsening. As in this case demonstrates, most myocarditis is curable and invasive measures are very helpful in rescuing patients from the fulminant type with refractory Vf.

Anticoagulants↗

Antinociceptive effect of the combination of pentazocine with morphine in the tail-immersion and scald-pain tests in rats.

We investigated the antinociceptive effect of pentazocine hydrochloride (pentazocine) in combination with morphine hydrochloride (morphine) using two antinociceptive tests; i.e., the tail-immersion and scald-pain tests, in rats. In the tail-immersion test, the rat's tail was immersed in warm water at 47 degrees C, and the latency to a nociceptive response was measured. In the scald-pain test, the right hind foot was scalded by immersion into hot water at 57 degrees C. Two hours later, additional thermal stimulus was applied to the same foot, and the latency to a nociceptive response was measured. Subcutaneous treatment with either pentazocine (6, 12, 24 mg/kg) or morphine (1.5, 3, 6 mg/kg) alone dose-dependently showed antinociceptive effects in both tests. The ED50 values (95% confidence limit) of pentazocine and morphine were 13.0 (5.4-31.5) and 2.4 (1.6-3.7) mg/kg in the tail-immersion test and 11.0 (4.5-26.6) and 3.8 (1.8-7.2) mg/kg in the scald-pain test, respectively. Simultaneous treatment with pentazocine at the similar dose augmented the morphine (1.5 mg/kg)-induced antinociception, but did not diminish the morphine (6 mg/kg)-induced antinociception in both tests. These results suggest that the simultaneous administration of pentazocine at the antinociceptive dose and morphine exerts additional antinociceptive activity against thermal and scald-induced inflammatory pain.

Analgesics, Opioid↗