Advanced glycation end products are associated with beta 2-microglobulin amyloidosis.
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Amyloidosis↗
Biomedical subjects
Y Koda
Publications and source records attributed to Y Koda.
Application of curdlan to controlled drug delivery. III. Drug release from sustained release suppositories in vitro.
The use of curdlan, a natural beta-1,3-glucan, in the preparation of sustained release suppositories was studied in vitro. To prepare the suppositories, indomethacin, prednisolone or salbutamol sulfate was mixed with curdlan gel. Preparation conditions, including heating time and curdlan concentrations of 5 and 10%, had little effect on the drug release. The tonicity (hypotonic or isotonic) of the media for the suppository preparation and for in vitro drug release study also had little effect on drug release. However, the heating temperature during gel preparation, the drug amount in the suppository and the type of release media did affect drug release. It was found that drug release was sustained and diffusion-controlled in the three drugs. And finally, curdlan can be applicable for use in a sustained release suppository.
Albuterol↗
Detection of G to A missense mutation of Lewis-negative gene by PCR on genomic DNA.
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Base Sequence↗
Analysis of Lewis fucosyltransferase genes from the human gastric mucosa of Lewis-positive and -negative individuals.
The expression of Lewis fucosyltransferase (FT) mRNA was examined in gastric mucosa from two Lewis-positive [Le(+)] and two Lewis-negative [Le(-)] individuals. Northern blot analysis demonstrated that levels of mRNA were similar in both Le(+) and Le(-) gastric mucosa. We isolated the protein-coding region of the Lewis FT cDNA from Le(+) and Le(-) gastric mucosa by polymerase chain reaction (PCR) amplification. The sequence of cDNA from the Le(-) gastric mucosa shows two single-base substitutions of G for T at position 59 and of A for G at position 508 from the A of the initiation codon of cDNA. These substitutions may be the cause of changes in two amino acid residues, Arg for Leu at position 20 and Ser for Gly at position 170 from the N-terminal. To determine whether either or both of these base substitutions is responsible for the Le(-) gene, we constructed chimera cDNAs and expressed them in COS cells. Those COS cells transfected with a chimera cDNA containing a mutation of the 508th nucleotide did not express Lewis antigen, whereas those cells transfected with a chimera cDNA containing the 59th nucleotide mutation expressed Lewis antigen, indicating that a single-base change from G to A at position 508 is responsible for the Le(-) gene. The G to A transition at position 508 created a new site for PvuII endonuclease. The digestion by PvuII endonuclease of PCR products between the 386th and 612th nucleotides of Lewis FT cDNA from one of the Le(-) individuals proved to be homozygous for the PvuII site. However, the other Le(-) individual was heterozygous for the PvuII site, suggesting the presence of other Le(-) allele(s). Thus, we isolated one of the silent Lewis genes (le).
Amino Acid Sequence↗
Rubinstein-Taybi Syndrome with thymic hypoplasia.
We report the autopsy findings in a 20-month-old boy with Rubinstein-Taybi syndrome and DiGeorge sequence. No visible thymus was demonstrated at the time of autopsy. With careful microscopic examination, a few pieces of thymic tissues found near the thyroid gland showed remarkable depletion of both thymocytes and cortical epithelial cells. Immunohistological staining with T-cell surface antigens resulted in a definite positive reaction. Repeated respiratory infections present in this patient may, in part, be attributable to thymic hypoplasia. Other major anomalies included broad thumbs and great toes, microphthalmia, arrhinencephaly, patent ductus arteriosus, stenosis of the ureterovesicular junction, bilateral cryptorchidism, and minor facial anomalies.
DiGeorge Syndrome↗
Jasmonic acid-inducible gene expression of a Kunitz-type proteinase inhibitor in potato tuber disks.
Messenger RNAs of a potato (Solanum tuberosum L.) Kunitz-type proteinase inhibitor(s) (PKPI) were present in potato disks excised from tubers stored for 14 months (old tubers) or 2 months (young tubers) after harvest, and disappeared during the aseptic culture. The PKPI mRNA accumulation was found to be induced in potato disks from the old tubers by the addition of jasmonic acid (JA) [3-oxo-2-(2'-cis-pentenyl)-cyclopentane-1-acetic acid].
Cyclopentanes↗
Changes in carpal tunnel shape during wrist joint motion. MRI evaluation of normal volunteers.
This study evaluated dynamically the morphology of the carpal tunnel during the wrist motion. The object was to determine the transverse dimension (TD), anteroposterior (AP) dimension and cross-sectional area (CA) of the carpal tunnel in the neutral, flexed and extended positions. The wrists of eight male and eight female volunteers aged 20 to 38 years were studied. With wrist extension, AP and CA decreased while the TD increased at the pisiform level, and CA increased at the hamate level. With flexion, TD and CA decreased at the pisiform level and CA decreased at the hamate level. The results showed that the median nerve may be subjected to significant pressure at the pisiform level when the wrist is extended. During wrist flexion, the cross-sectional area decreased at both the level of the pisiform and the hook of the hamate.
Adult↗
[Clinical pharmacology and efficacy of S-1108].
We studied the pharmacokinetics of a new cephem antibiotic, S-1108, in patients with impaired kidney functions. Serum and urinary levels of S-1006 were determined after oral administration of S-1108 at 150 mg to 9 patients with renal dysfunction. In patients with severe renal impairment, high serum levels were maintained over long periods of time. Urinary excretion rates of S-1006 were lower as degrees of kidney failure were severer. S-1108 was administered to treat 27 patients with respiratory tract infections, and its clinical efficacy and safety were evaluated. The clinical efficacies were good in 26 patients, but poor in 1, yielding an efficacy rate of 96.3%. As to adverse reactions; diarrhea was observed in one case. Laboratory tests revealed elevated GOT and GPT in 1, and elevated gamma-GTP in another. These abnormalities, however, were slight and no severe side effects were caused by the drug.
Administration, Oral↗
[Clinical evaluation and pharmacology of DQ-2556 in the patients with compromised renal function].
We studied the pharmacokinetics of a new cephem antibiotic, DQ-2556, in patients with impaired kidney function. The peak concentrations of the compound in the serum were observed irrespective of the degree of kidney failure 5 minutes after its bolus administration of 1.0 g intravenously, and no significant difference was observed in the concentrations among the patients. On the other hand, the decrease in its concentrations in the serum was impeded in proportion to degrees of kidney failure and, in particular, hemodialysis patients showed markedly delayed clearance of the drug from the serum; the half-lives in the serum (beta phase) were prolonged to ca. 6 hours in patients with severe kidney failure (Ccr ca. 20 ml/min) and did so markedly to ca. 17 to 21 hours in patients with hemodialysis as compared with ca. 2.5 hours in patients with slight kidney failure (Ccr ca. 50 ml/min). Urinary excretion rates (0-to-24 hours values) were ca. 70% in patients with slight kidney failure, ca. 60% in patients with moderate kidney failure and ca. 40% in patients with severe kidney failure, showing a tendency toward a decline in relation to increasing degrees of kidney failure. The compound showed a satisfactory dialytic property. The clinical efficacy and safety of DQ-2556 were evaluated upon administering if at daily doses of 0.5 g b.i.d. and 1.0 g b.i.d. for 7 and 14 consecutive days respectively, in patients with lower respiratory tract infections. The clinical efficacies were excellent in 2 patients, good in 11 and poor in 2, yielding a efficacy rate of 86.7%. No side effects were observed, though, a neutrophil sedimentation ratio decreased in a patient, and a down-shift of prothrombin activities was observed in another. These results suggest that DQ-2556 is useful for lower respiratory tract infections, but in patients with kidney failures it is required to seek the most suitable regimen since the excretion rates of the compound decrease as degrees of kidney failure become severer.
Adult↗
[Clinical significance of urinary methylguanidine in non-dialyzed patients with chronic renal failure--prediction of progression rate of renal dysfunction].
To clarify a clinical significance of urinary methylguanidine (U-MG, micrograms/dl) in non-dialyzed patients with chronic renal failure, we measured U-MG, urinary creatinine (U-Cr, mg/dl) and serum creatinine (S-Cr, mg/dl), concurrently and continually in 36 out-patients whose S-Cr was over 4.0 mg/dl. Fresh urine sample was obtained and U-MG was measured by an enzymic method. S-Cr concentrations (mean +/- SD) at the initiation of dialysis therapy were comparable in non-diabetics and in diabetics, being 13.4 +/- 4.54mg/dl and 8.23 +/- 1.96mg/dl, respectively, with statistical significance (p < 0.01). U-MG/Cr (micrograms/mg. Cr) values were also different between them, being 9.28 +/- 4.97 in non-diabetics and 5.19 +/- 1.29 in diabetics, but with lesser statistical significance (p < 0.05) than S-Cr. U-MG/Cr correlated well with the terms till the initiation of dialysis therapy (r = 0.7189, p < 0.001), more significantly than S-Cr (r = 0.5506, p < 0.001) in parabolic regression analysis. U-MG/Cr were greatly varied among the 7 patients, although whose S-Cr was nearly the same level (6.0-6.9mg/dl). Most importantly, the tendency was found in these patients that the higher U-MG/Cr, the earlier the renal replacement therapy instituted. These results suggests that U-MG/Cr can be reliable parameter to predict the progression rate of renal failure and to help to know when renal replacement therapy should be instituted.
Adult↗
Veratridine causes the Ca(2+)-dependent increase in diacylglycerol formation and translocation of protein kinase C to membranes in cultured bovine adrenal medullary cells.
Our previous studies suggested that protein kinase C is involved in the veratridine (an activator of voltage-dependent Na+ channels)-induced phosphorylation and activation of tyrosine hydroxylase as well as the synthesis of catecholamines in adrenal medulla (Uezono et al. 1989). In the present study, we investigated whether treatment of cultured bovine adrenal medullary cells with veratridine causes the accumulation of diacylglycerol, a physiological activator of protein kinase C and the translocation of protein kinase C from cytosol to membrane, a process required for protein kinase C activation. Veratridine (100 mumol/l) increased diacylglycerol level about 2.2 fold in a monophasic manner, with peaking at 5 min and declining toward the basal level within 20 min. Veratridine also increased membrane protein kinase C from 15.6% to 26.9% of total protein kinase C in a time-course similar to that of diacylglycerol accumulation. Both stimulatory effects of veratridine were inhibited by tetrodotoxin and not observed in Ca(2+)-free, EGTA-containing medium. Amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchange, did not alter veratridine-induced events. These results suggest that veratridine-induced Ca2+ influx contributes to the accumulation of diacylglycerol and the activation of protein kinase C in adrenal medullary cells.
Adrenal Medulla↗
The role of jasmonic acid and related compounds in the regulation of plant development.
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Cyclopentanes↗
Application of curdlan to controlled drug delivery. I. The preparation and evaluation of theophylline-containing curdlan tablets.
To study the use of curdlan, a natural beta-1,3-glucan, in drug delivery, in vitro release studies were carried out with curdlan tablets containing theophylline. Tablets were readily prepared by compressing three different curdlan and theophylline mixtures, namely, a physical mixture, spray-dried curdlan particles with theophylline powder, and spray-dried particles of curdlan/theophylline solution. Drug release from the tablets prepared from spray-dried particles of curdlan/theophylline was lowest. The release rate was constant from 1 to 8 hr, and 59% cumulative release was obtained at 8 hr. Drug release from curdlan tablets was unaffected by pH or various ions; these curdlan tablets might also control drug release in vivo after oral administration. Application of Higuchi's equation indicated that drug release from curdlan tablets was diffusion-controlled. The release profiles of the curdlan tablets were compared to those of a commercial theophylline sustained-release tablet.
Chemistry, Pharmaceutical↗
[Clinical pharmacology and efficacy of levofloxacin in elderly patients].
We studied a newly developed oral quinolone antimicrobial agent, levofloxacin (LVFX, DR-3355), and obtained the following results. 1. Serum and urine levels of LVFX were determined after oral administration of LVFX 100 mg to 11 elderly patients with various degrees of renal function insufficiencies. The patients were classified according to creatinine clearance (Ccr) values into Group I (n = 1, Ccr greater than or equal to 70 ml/min), Group II (n = 4, 40 less than or equal to Ccr less than 70 ml/min), and Group III (n = 6, Ccr less than 40 ml/min). The peak levels of LVFX did not differ greatly among the 3 groups, but in patients with severely impaired renal functions, serum concentrations decreased more slowly than in those with slightly and moderately impaired renal functions, and high serum levels were maintained over a long period. Urinary excretion of LVFX diminished in relation to degrees of renal failure. 2. LVFX was administered to treat 13 elderly patients with respiratory tract infections. Clinical responses were good in all patients with a high efficacy rate of 100%. Laboratory tests revealed eosinophilia in 1 case. The symptom was mild, however, and no severe side effects due to the drug were observed.
Aged↗
Protein kinase C in human pheochromocytoma.
Subtypes of protein kinase C were analyzed in adrenal and extra-adrenal pheochromocytoma of humans. Almost all protein kinase C of the adrenal tumor was type III, while the enzyme of the extra-adrenal tumor was separated into two major fractions corresponding to type II and type III by hydroxyapatite column chromatography. The extra-adrenal tumor but not the adrenal tumor spontaneously produced neurite-like processes when the cells were cultured in vitro. These results suggest that the high proportion of type II enzyme may reflect neuron-directed differentiation in human pheochromocytoma.
Adrenal Gland Neoplasms↗
Subtypes of protein kinase C in rat cerebral microvessels.
Protein kinase C in rat cerebral microvessels was characterized. By hydroxyapatite column chromatography, protein kinase C in the soluble fraction was resolved into two major peaks corresponding to type II and III enzymes, in the proportion of 57% and 38%, respectively. Since each subtype is considered to have a distinct role, the high proportion of type II enzyme found in this study suggests that this type may be involved in specific functions of the cerebral microvessels.
Animals↗
Inhibitory effect of okadaic acid on carbachol-evoked secretion of catecholamines in cultured bovine adrenal medullary cells.
We examined the effect of okadaic acid on catecholamine secretion caused by carbachol in cultured bovine adrenal medullary cells. Treatment of cells with 100 nM okadaic acid for 3-24 hr produced an inhibition of catecholamine secretion stimulated by carbachol. The half-maximal and maximal inhibition of secretion was observed at 40 nM and 300 nM okadaic acid for 24 hr, respectively. Okadaic acid also inhibited veratridine- and high K(+)-induced secretion but not ionomycin-induced secretion. Okadaic acid strongly suppressed 45Ca2+ influx and slightly inhibited 22Na+ influx in carbachol-stimulated cells. These results suggest that okadaic acid inhibits carbachol-evoked secretion of catecholamines mainly by suppression of Ca2+ influx in adrenal medullary cells.
Adrenal Medulla↗
Development of a new antithrombogenic continuous ultrafiltration system (ACUS) and its clinical evaluation.
A new totally antithrombogenic continuous ultrafiltration system (ACUS), consisting of polyacrylonitrile-polyethyleneoxide (PAN-PEO) membrane and ionically heparin-bound catheter, tubing, and module header was designed and its performance was confirmed through animal experiments and clinical evaluation. Animal experiments revealed that persistent antithrombogenicity and maintained ultrafiltration without systemic heparinisation were observed only when the three major parts--i.e. (1) the catheter and tubing, (2) the header part of a haemofilter module, and (3) the fibre membrane--were all antithrombogenic and connected to each other without uneven structures. ACUS was clinically applied to 15 oliguric patients with various severe conditions. We found that one filter could function for approximately 26 h without systemic anticoagulation, even in the presence of low blood pressure, and that ACUS did not change platelet function. Thus, ACUS seems to be very suitable for the management of volume overload, especially in patients with severe circulatory problems or bleeding tendencies.
Acrylic Resins↗