Search PubMed⌕ Search

Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 955 records · Page 53Linked to original sources

Computer-aided analysis of Z-plasties.

Various Z-plasties were evaluated with a mathematical analytical method called the finite-element method. The lengthening and shortening effects on the skin proved to depend on the tip angle. Serial Z-plasties diminished the stress concentration after pairs of flaps had been transposed. Subdivided Z-plasties proved to be the most effective for lengthening. The finite-element method provided a good simulation of Z-plasties on a skin with complex properties. The lengthening and shortening effects on anisotropic skin were influenced not by the degree but by the direction of the anisotropy, whereas the total force required for transposing the two flaps was vice versa. The finite-element method was found to be useful for finding analytical solutions for biomechanical skin problems.

Animals↗

Unstable cervical spine in athetoid cerebral palsy.

The manifestations and pathomechanism of cervical instability of the athetoid neck in cerebral palsy (CP) patients was clarified in this study by means of static and dynamic x-ray analysis. Instability was defined as follows: 1) listhesis indicating anterior or posterior slip of more than 3 mm and/or 2) sagittal rotation between two vertebrae beyond the normal range measured by Penning. Cervical instability fitting this definition mainly took place in the upper and middle cervical disc levels, such as C3-4, C4-5, and/or occasionally C5-6. These coincide with the disc levels adjacent to the apex of the lordotic curve and/or those around the transitional vertebrae between the two reversed curves that render the cervical spine S-shaped in athetoid CP. A large facet angle at the apex vertebra facilitated anterior and/or posterior listhesis of the vertebrae. Conversely, a sudden decrease in the facet angle around the transitional vertebra in S-shaped curves precipitated deflection of the spine and increased sagittal rotation at this level. In addition to these structural abnormalities, rapid and repetitious neck movements seemed to accelerate the progression of cervical instability in athetoid CP patients.

Athetosis↗

Transcriptional regulation of F plasmid gene srnB: rifampicin-promoted in vitro readthrough of a terminator in the leader region.

srnB is an F-plasmid encoded gene, otherwise silent, whose expression is induced by added rifampicin, leading to the release of cellular Mg2+ and degradation of stable RNA. In the absence of rifampicin, transcripts from the srnB gene were relatively short. S1 nuclease mapping revealed that the short mRNA species terminated within the leader, at the 3' end of a potential stem-and-loop structure. A deletion in the stem-loop resulted in constitutive synthesis of the mRNA that extended beyond the termination site into the structural gene. Even with the wild-type gene, transcription continued beyond the terminator sequence in the presence of added rifampicin. Most of the transcripts synthesized in the presence of rifampicin were long enough to encode the srnB protein. We hypothesize from these results that RNA polymerase associated with rifampicin can read through the terminator to induce srnB expression.

Amino Acid Sequence↗

The pharmacokinetics and pharmacodynamics of a new thromboxane synthetase inhibitor, 6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (DP-1904), in man after single oral administration.

The pharmacokinetics of DP-1904, a new potent and selective thromboxane synthetase inhibitor and its effects on ex-vivo prostanoid formation were studied in Japanese normal male volunteers, who received orally a single 10, 20, 50, 100, 200, 400 or 800 mg dose. The drug was well tolerated by all subjects without evidence of any adverse reactions. The absorption of DP-1904 from gastro-intestinal tract was rapid. After oral doses of 10-800 mg of the drug given to volunteers in the fasted state, the mean maximum drug concentrations in plasma (Cmax) (mean +/- s.e., n = 5) of 0.215 (+/- 0.041), 0.399 (+/- 0.037), 1.47 (+/- 0.22), 2.86 (+/- 0.22), 4.66 (+/- 0.58), 7.28 (+/- 0.72) and 16.9 (+/- 2.6) micrograms mL-1 were reached within 1 h. DP-1904 concentrations declined monophasically after Cmax with half lives of 30-40 min. These half lives were independent of the administered doses. The mean area under the concentration-time curves (AUCs) increased from 0.398 (+/- 0.038) to 30.0 (+/- 2.7) micrograms h mL-1 as the dose increased from 10 to 800 mg. Linear relations between the doses and Cmax and AUCs were observed. The correlation coefficients for Cmax and AUC were 0.930 and 0.960, respectively. The apparent oral clearance (CL/F) and renal clearance (CLR) did not change significantly as dose increased from 10 to 800 mg. The kinetics of DP-1904 proved to be linear in the dose range studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Preparation of drug-diluent hybrid powders by dry processing.

New hybrid powders have been produced by the dry processing of six drugs (oxyphenbutazone, prednisolone, theophylline, indomethacin, phenacetin and aspirin), with potato starch used as a core material, by means of an electric mortar and a powder surface reforming system designed to produce hybrid powders. The hybrid powders obtained immediately after production differed in their structure from interactive mixtures. With the hybrid powders the drug was spread on the surface of the core particle by friction and collision that occurred in the dry process, but with interactive mixtures the drug simply adhered as intact particles to the surface of diluent particles. Scanning electron microscopy and powder X-ray diffractometry indicated that the mechanochemical phenomenon was essential for the production of the hybrid powders. With time, a shape change in the adhering drug was observed as a relaxation process took place, with recrystallization resulting from the release of accumulated energy. The change with time might depend upon the method of producing powders and the physical properties of the drug used, e.g. the smooth layer of indomethacin produced by the powder surface reforming system reverted to fine particles tightly adhering to the starch surface, though no change was observed with prednisolone.

Chemistry, Pharmaceutical↗

Modulation of the delayed rectifier K+ current by isoprenaline in bull-frog atrial myocytes.

1. The effects of isoprenaline (ISO) on the calcium current (ICa) and delayed rectifier K+ current (IK) were examined using a tight-seal whole-cell voltage-clamp technique in single cells from bull-frog atrium to examine the ionic mechanism(s) of catecholamine-induced action potential shape changes. 2. The effects of ISO on the action potential were dose-dependent. Very low doses (5 x 10(-9) M) prolonged the action potential. Higher doses (10(-6) M) of ISO increased the plateau height, but shortened the action potential by accelerating the early repolarization phase. 3. ISO increased IK and ICa in a dose-dependent fashion. Both of these effects were blocked by a beta-receptor antagonist, propranolol (3 x 10(-7) M). In contrast IK1, the inwardly rectifying K+ current, was not changed significantly by ISO. 4. The ISO-induced increase in IK was observed in the presence of CdCl2 (3 x 10(-4) M), indicating that this effect is not due to a Ca2(+)-activated potassium current. 5. The reversal potential of IK in normal Ringer solution (-83 +/- 2 mV) was not significantly changed by ISO. Thus, stimulation of the Na(+)-K+ pump and a consequent hyperpolarizing shift in EK are not responsible for the increase in IK. 6. In the presence of ISO (10(-6) M) the steady-state activation curve (n infinity) for IK was consistently shifted to more negative values (by approximately 10 mV). The activation and deactivation kinetics of IK were also changed by ISO: activation was accelerated, deactivation was slowed. These ISO-induced changes in IK result in an increase in IK at voltages corresponding to the plateau of the action potential. 7. ISO (10(-6) M) increased ICa dramatically, approximately 6-fold at 0 mV. At the same time, the time constant of ICa inactivation decreased significantly (34 +/- 4 ms control; 23 +/- 4 ms ISO). 8. These results confirm that low doses of sympathetic agonists acting via beta-receptors increase ICa. Relatively high doses of beta-receptor agonists increase both ICa and IK, but these two effects appear to be generated by different biophysical mechanisms. 9. These dose-dependent changes in ICa and IK can explain the observed ISO-induced changes in action potential shape. At doses of approximately 10(-8) M ICa is increased, resulting in a more depolarized plateau and small lengthening of the action potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

[Hepatitis B vaccination in alcoholics].

The immune response after HB vaccination (20 micrograms, 3 times) was investigated in 15 alcoholics and the immunological background was also studied before the vaccination in some of these cases. Anti-HBs was detected in only 8 (53.3%) out of 15 vaccinated alcoholics and the anti-HBs titers of these 8 responders were less than 16 cut off index at the last observation. Immunologically, peripheral lymphocyte count and/or the OKT4/OKT8 ratio of lymphocytes in 2 alcoholics (non-responders to vaccination) were lower than those in a control case (good responder). But, there were no differences in serum anti-HAV, anti-EBNA positive rates, immunoglobulin levels and blastogenesis by PHA, Con-A between responders and non-responders. These data suggest that poor response to HB vaccination is probably due to an impaired cellular immunity in alcoholics and the necessity of re-vaccination for no or low responders should be considered.

Adult↗

Isoproterenol, DBcAMP, and forskolin inhibit cardiac sodium current.

We studied the effects of isoproterenol (ISP), dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), and forskolin on the sodium current (INa) of guinea pig ventricular myocytes using the tight-seal, whole cell voltage-clamp method. The extracellular [Na+] [( Na+]o) was decreased to 60 mM by replacing NaCl with sucrose (temperature, 32-33 degrees C). Ionic currents other than Na+ were suppressed using appropriate channel blockers. Depolarizing clamp pulse (duration, 30 ms) was applied at a rate of 0.2 Hz from a holding potential of -80 mV. ISP (1 microM) decreased the peak INa by 34% from 6.1 +/- 1.9 (SD) nA (control) to 4.0 +/- 1.5 nA (n = 7). The inhibition was more prominent at less negative potentials and disappeared in the presence of a beta-blocker (10 microM atenolol). The effects of DBcAMP (1-5 mM) and forskolin (3 microM) mimicked those of ISP and depressed the peak INa reversibly. DBcAMP (5 mM) shifted the inactivation curve of INa [h infinity-membrane potential (Em) relationship] to a hyperpolarizing direction, by 3.4 +/- 0.8 mV (n = 5). These findings suggest that ISP inhibits the cardiac INa+, probably by altering the gating mechanism of the Na+ channel, and that the effect is secondary to the increased levels of intracellular cAMP, with possible acceleration of cAMP-dependent phosphorylation of the channel.

Animals↗

Intracellular localization of tyrosine hydroxylase immunoreactivity in the rat adrenal chromaffin and pheochromocytoma cells.

The localization of tyrosine hydroxylase (TH) immunoreactivity in rat adrenal chromaffin and pheochromocytoma (PC12) cells was investigated by immunoelectron microscopy using monoclonal and polyclonal antisera against TH purified from rat adrenal medulla. Strong TH immunoreactivity was found uniformly in the granules of the adrenaline cells; the immunoreactivity was visible mainly within the periphery, but not in the clear space of the granules of the noradrenaline cells. In the PC12 cells, strong TH immunoreactivity was also observed uniformly in the granules. In addition, TH immunoreactivity was seen in the cytoplasm, the ribosomes attached to the endoplasmic reticulum and the free ribosomes of both the rat adrenal chromaffin and PC12 cells. These results suggest that TH may be localized in the granules, cytoplasm and ribosomes of rat adrenal chromaffin and PC12 cells.

Adrenal Gland Neoplasms↗

Tyrosine-hydroxylase-immunoreactive nerve fibers in the separated capsule of the rat adrenal gland.

The present study applied the separated adrenal capsules of rats for wholemount immunocytochemistry and used tyrosine hydroxylase (TH) antibody as a marker for catecholamines. TH-immunoreactive nerve bundles without varicosities and fibers with varicosities were seen to run along or to encircle blood vessels entering the adrenal capsule from the outside, and then to run along a network of blood vessels in the intracapsular region. Also, the TH-immunoreactive nerve bundles and fibers were found to run along blood vessels in the subcapsular region. Some TH-immunoreactive nerve fibers and bundles with varicosities, unassociated with the blood vessels, were seen in the subcapsular region. In this region, TH-immunoreactive nerve fibers with varicosities were often seen to be closely associated with the cortical cells. Some TH-immunoreactive nerve fibers without varicosities were visible within the splanchnic nerve in the subcapsular region. The present study suggests that numerous catecholaminergic nerve fibers are associated with blood vessels forming a network in the superficial region of the rat adrenal gland.

Adrenal Glands↗

Acquired renal cysts in five-sixths nephrectomized rats: the roles of oxalate deposits in renal tubules and a renotropic factor.

The present study was undertaken to see if the oxalate deposits seen in renal tubules are a causative factor in the development of acquired renal cysts in chronic renal failure. Thirty 5/6 nephrectomized rats had free access to water containing 8 mg/ml of vitamin C (oxalate precursor) and 20 5/6 nephrectomized rats were given tap water without vitamin C. Oxalate deposits were found on microscopy in the renal tubules of vitamin C-treated rats in the 11th and 12th postnephrectomy months; however, acquired renal cysts were noted far in advance of the appearance of oxalate crystals. It has been suggested that the tubular dilatation seen in 5/6 nephrectomized rats is caused by an abrupt decrease in the functioning renal mass, leading to the production of a so-called 'renotropic factor'. However, oxalate deposits and renal tubular dilatation in oxalate-treated 5/6 nephrectomized rats preceded the renal tubular dilatation of untreated partially nephrectomized rats. In addition, these histological changes in the kidney were also seen in healthy rats which were given oxalate orally and subcutaneously. The present study suggested that the pathogenesis of acquired renal cysts is multifactorial. Renotropic factor may play an important role leading to nephron hyperplasia, but oxalate deposits in the renal tubules seem to be an important factor in the formation of these cysts.

Animals↗

Effect of vitamin C supplementation on renal oxalate deposits in five-sixths nephrectomized rats.

We have previously reported that hyperoxalemia can be aggravated by vitamin C supplementation in regular hemodialysis patients. The present study was undertaken to examine the validity of this observation in an experimental setting. Fifty five-sixths nephrectomized rats were divided into two groups: 30 rats were allowed free access to water containing 8 mg/ml of vitamin C (100-160 mg/100 g/24 h) and the remainder given tap water without vitamin C. The serum creatinine increased and the Hct decreased gradually; however, there was no difference between the two groups. Plasma vitamin C, oxalate and urinary oxalate levels were higher in the vitamin -treated group than the nontreated rats. Histological examination revealed glomerular and interstitial fibrosis and round cell infiltration as well as tubular cyst formation. Oxalate deposits in renal tubules were found only in vitamin C-treated rats with advanced renal failure. Nontreated animals with equally advanced renal impairment showed no oxalate deposits. These results confirm our previous clinical findings that vitamin C supplementation aggravates the secondary oxalosis of chronic renal failure.

Animals↗

Abnormalities in the hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats during development of hypertension.

Abnormalities in the hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats (SHR) during development of hypertension were investigated using in vivo and in vitro methods. Plasma ACTH responses to hemorrhage and ether stress were significantly smaller in 7-week-old SHR than in age-matched Wistar-Kyoto rats (WKY), while plasma corticosterone baseline levels and its response to stress were greater in SHR than in WKY. There was no significant difference in the plasma ACTH response to ether stress between bilaterally adrenalectomized SHR and WKY replaced with a 25% corticosterone pellet for 6 days. Adrenalectomy prevented the development of hypertension in SHR; however, corticosterone replacement restored hypertension. Plasma ACTH showed a smaller response to iv CRH injection in SHR than in WKY, while the ACTH response to arginine vasopressin was not different between SHR and WKY. CRH concentrations in the median eminence, posterior pituitary, and cerebral cortex were lower in SHR than in WKY, while the CRH concentration in the median eminence was not different in SHR and WKY when they were adrenalectomized with or without corticosterone replacement. Basal in vitro CRH release from hypothalamic tissue was reduced in SHR, while CRH release in response to 56 mM KCl was not different in SHR and WKY. These results suggest that adrenocortical function is enhanced in young SHR, that reduced ACTH response to stress and exogenous CRH in SHR may be ascribed to higher plasma corticosterone levels, and that corticosterone is essential for the development of hypertension in SHR.

Adrenalectomy↗

Differential inhibitory effects of various herb extracts on the activities of reverse transcriptase and various deoxyribonucleic acid (DNA) polymerases.

Forty preparations of the extracts from 28 kinds of Asian herbs were tested for ability to inhibit the activities of murine retroviral reverse transcriptase and human deoxyribonucleic acid (DNA) polymerases. Among the 40 extracts, 35 inhibited reverse transcriptase activity and 29 inhibited DNA polymerase alpha activity. The inhibitory potencies of these extracts were expressed as the 50% inhibition concentrations (IC50), at which the enzyme activities were inhibited by 50%. Very strong inhibitions were observed with the extracts from Millettia pachycarpa (Leguminosae) and Mallotus apelta (Euphorbiaceae) as shown by their low IC50 values for reverse transcriptase (0.4-0.5 micrograms/ml) and DNA polymerase alpha (0.9-1.4 micrograms/ml). Enzyme kinetic analysis revealed that the mode of inhibition of reverse transcriptase by these two extracts was competitive with respect to the template.primer [poly(rA).oligo(dT)] and noncompetitive with respect to deoxythymidine triphosphate (dTTP) substrate. Besides reverse transcriptase and DNA polymerase alpha, DNA polymerase I and ribonucleic acid (RNA) polymerase from E. coli were inhibited by these two extracts. These results indicate that the herb extracts contain as yet unidentified substance(s) which inhibit the activities of reverse transcriptase and cellular DNA polymerases.

Humans↗

The microheterogeneity of bovine serum alpha 1-acid glycoprotein.

The microheterogeneity in bovine serum alpha 1-acid glycoprotein (alpha 1AGP) was examined by crossed affino-immunoelectrophoresis with concanavalin A(Con A). In healthy cows, serum alpha 1AGP revealed 2 fractions which were named fraction 1 and 2 according to the degree of binding affinity to Con A. The mean +/- SD of serum alpha 1AGP concentration was 0.31 +/- 0.09 g/l and the relative amounts of fraction 1 and 2 were approximately 67% and 33% respectively on this method. In bovine leukemia cases, 5 out of 8 had a high serum alpha 1AGP concentration of more than 0.7 g/l. On the electrophoretic pattern, the other 2 fractions (Con A weakly and non-reactive fractions, named fraction 3 and 4) were observed in 5 cases and their relative amounts of 4 fractions were 17.8-28.5%, 35.5-46.0%, 17.9-24.4% and 12.0-17.2%, respectively. In bovie leukemia virus infected cows with no clinical symptoms, however, serum alpha 1AGP concentration and the electrophoretic patterns were almost the same as those in healthy cows.

Animals↗