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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 1,063 records · Page 59Linked to original sources
PubMed1991

[Retention of amorolfine in the skin tissue as measured by prevention of the development of experimental dermatophytosis in guinea pigs].

In order to assess the extent of dermal retention of amorolfine (MT-861), a new morpholine antifungal agent, cream preparations of MT-861 were applied to the skin on the back of guinea pigs and the protective effect was determined regarding the topical treatment on the development of infection induced by subsequent inoculation with conidia of Trichophyton mentagrophytes. One per cent bifonazole (BFZ) cream was used as the reference drug. The results are summarized as follows. 1. Pretreatment with 0.125, 0.25 or 0.5% MT-861 preparation 1 to 3 days before infection significantly reduced the extent of lesion developed compared to the untreated control at postinfection day-12 and day-19 measurements. 2. Cultures of specimens taken from the skin lesion performed on postinfection day-19 showed that pretreatment with 0.125, 0.25 or 0.5% MT-861 cream 1 day before infection significantly lowered the number of culture-positive skin lesions compared to that of untreated control. 3. No significant difference was observed among the 3 experimental groups of animals pretreated with MT-861 preparations 1 to 3 days before infection in extent of lesions developed, though the mycological protective effect of the drug appeared to decrease with increasing time intervals between drug-pretreatment and fungal challenge. 4. A 0.5% MT-861 preparation had an equal or superior infection-preventive effect to 1% BFZ preparation as far as severity of lesion and recovery of fungi were concerned. 5. The potent and prolonged protective action by MT-861 preparations against the development of fungal infection strongly suggests that MT-861 retains in the skin tissue in an active from for substantially long periods of time.

Animals↗
PubMed1991

[In vitro antifungal activity of amorolfine, a new morpholine antimycotic agent].

In vitro antifungal activities of amorolfine (MT-861), a newly developed morpholine antimycotic agent, against a wide range of pathogenic fungal strains were investigated using an agar-dilution method with an imidazole antifungal agent, clotrimazole (CTZ), as the reference drug. The results showed that MT-861 had a broad antifungal spectrum, and was active against all of the pathogenic fungi tested except nonpigmented filamentous fungi such as aspergilli and penicillia. Dermatophytes and Malassezia furfur was the most highly susceptible to MT-861. Antifungal activities of MT-861 against most strains of these fungi as well as those against most strains of dimorphic fungi were higher than those of CTZ. By contrast, MT-861 showed lower activities against pathogenic yeasts such as Candida albicans than CTZ. Several assay conditions, such as inoculum size of fungi, incubation time, media pH and compositions including serum supplementation, affected MT-861 activities against C. albicans and, to lesser extents, those against Trichophyton mentagrophytes. MIC values of MT-861 against C. albicans and other Candida spp., were the lowest on casitone agar. MT-861 exerted fungicidal actions toward susceptible fungi such as T. mentagrophytes and Sporothrix schenckii at relatively low concentrations, and these activities were increased when the time of incubation was extended beyond 24 hours after inoculation of testing organisms. Susceptibilities of any strains of C. albicans and C. glabrata to MT-861 were not reduced by as many as 15 successive transfers in MT-861 containing media.

Antifungal Agents↗
PubMed1991

[Outpatient treatment with extracorporeal lithotriptor for renal and ureteral stones].

Between April 1989 and December 1989, extracorporeal shock wave lithotripsy (ESWL) was performed on 78 outpatients using the EDAP LT-01 device without anesthesia. The locations of total 83 stones were renal pelvis and calyx (45), upper ureter (26) and lower ureter (12). Of the cases with renal stones, 28 (62%) were free of stones, and 8 (18%) had fragments 4 mm in size or less. The over-all successful rate obtained by combining these categories were 80% in renal stones, 81% in upper ureteral stones, and 92% in lower ureteral stones. As complications, gross hematuria, pain which required analgesics, fever of 38 degrees C or higher and vomiting were seen. However, no serious complications were observed.

Adolescent↗
PubMed1991

[Kinetics of PTH metabolism after total parathyroidectomy and autograft at forearm in patients with secondary hyperparathyroidism due to chronic renal failure].

Five patients with secondary hyperparathyroidism (2(0) HPT) due to chronic renal failure were investigated for PTH metabolism kinetics after total parathyroidectomy and autograft at the forearm (PTxG). We studied the kinetics of PTH for 24 hours after surgical treatment and gradually increased PTH levels when the parathyroid grafts became functional. It has been well known that the secreted intact PTH is peripherally cleaved in the region of reside 34 to yield amino- and carboxyl-terminal fragments. In this study, specific assays were used for intact PTH (INT-PTH), middle (HS-PTH, MM-PTH) and carboxyl-terminal (C-PTH) fragments. Half-lives were calculated from the mean values of all experiments by a two-compartment system; INT-PTH: 11.1 +/- 3.9 min, HS-PTH: 9.6 +/- 1.7 hrs., MM-PTH: 11.1 +/- 2.9 hrs., C-PTH: 10.1 +/- 1.2 hrs. (Mean +/- SD). The disappearance rate of biologically active intact PTH was rapid, whereas those of middle and carboxyl-terminal biologically inactive fragments were prolonged in the patients with chronic renal failure. The graft function was examined by PTH gradient between the venous samples in the grafted arm as compared to the non-grafted arm. PTH gradient of INT-PTH assay was over 1.5 one week following PTxG in all patients. This suggests that the intact PTH assay is a reliable predictor of clinical response to the graft function after PTxG.

Forearm↗
PubMed1991

[Dissecting aortic aneurysm associated with myonephropathic-metabolic syndrome and hypercalcemia].

A forty-two years old male underwent an aortic arch replacement for an emergency treatment of dissecting aortic aneurysm (DeBakey type I). Separate cardiopulmonary bypass was used with main arterial inflow cannula inserted to right femoral artery. After the operation, ischemia of the right lower extremity led to acute renal failure due to myonephropathic-metabolic syndrome. Peritoneal dialysis, hemodialysis, and continuous arterio-venous hemofiltration were performed. Renal failure improved gradually. At the diuretic phase serum calcium concentration began to rise. Inspite of large amount of fluid and furosemide injection it became higher and finally reached to 20 mg/dl level. Calcitonin injection (320 mu/day) was very effective. In 2 months after surgery serum creatinine and calcium concentrations went down to normal range. Abnormalities in calcium metabolism are frequent in rhabdomyolysis-induced acute renal failure. However, it is rare to encounter such a remarkable hypercalcemia as seen in this patient. When treating MNMS we should pay attention to the changes of serum calcium concentration.

Acute Kidney Injury↗
PubMed1991

[Effect of azosemide and furosemide on body fluid distribution and vasoactive hormones].

We examined the diuretic action of orally administered azosemide (AZ: 60 mg) and furosemide (FM: 40 mg) and their effects on body fluid distribution and circulatory vasoactive hormones in normal male volunteers. Urine volume and urinary sodium excretion were increased, peaking during 0 to 2 hours in FM and 2 to 4 hours in AZ in response to administration of both diuretics. The cumulative urine volume and urinary sodium excretion for 8 hours showed no significant difference between AZ and FM. Total body water (TBW) was measured by the dynamic distribution of deuterium oxide and a percentage change in circulating plasma volume (ICG ratio) was determined by using indocyanine green. The decrease in TBW and ICG ratio was detected in proportion to the increase in urine volume after administration of AZ and FM. Plasma renin activity (PRA) and plasma concentration of aldosterone (PAC), angiotensin II (ANG II) and arginine vasopressin (AVP) were elevated in response to the reduction in ICG ratio by both diuretics. The responses of PRA, PAC and ANG II to AZ were delayed about 2 hours as compared with those of FM. The increase in AVP with FM was significantly greater than that with AZ detected 2 hours after administration. The elevation of AVP in AZ was delayed and blunted compared with FM. These data indicate that the difference in diuretic property of AZ and FM may induce different stimulation to the secretion of vasoactive hormones through the changes in body fluid distribution and these hormones might modify the anti-edematic effect of AZ and FM.

Administration, Oral↗
PubMed1990

Effects of antiandrogens on growth of androgen-dependent mouse mammary tumor (Shionogi carcinoma 115) in vivo and in vitro.

Binding affinities of modified steroidal anthrasteroids, 3 beta-hydroxy-3a beta,6-dimethyl-2,3,3a,4,5,8,9,10,10a beta,11,11a beta, 11b alpha-dodecahydro-1H-cyclopenta[a]anthracene-8-one (1) and 3a beta,6-dimethyl-2,3,3a,4,5,8,9,10,10a beta,11,11a beta,11b alpha-dodecahydro-1H-cyclopenta[a]anthracene-3,8-dione (2), the steroid oxendolone and the nonsteroid AA560, for the androgen receptor (AR) of Shionogi carcinoma 115 (SC115) and their effects on the growth of SC115 were investigated in vivo and in vitro. The inhibitory effects of these compounds on testosterone 5 alpha-reductase of SC115 tissues were also measured. The relative binding affinities of these compounds were 3.17-0.03% of that of dihydrotestosterone, and their rank order was (1) greater than AA560 greater than oxendolone much greater than (2). In the presence of 10(-9) M testosterone, anthrasteroids and AA560 inhibited the growth of SC115 cells at 10(-7) M in a serum-free medium, but oxendolone did not. In the absence of testosterone, (1), (2) and oxendolone promoted cell growth at 10(-6), 10(-7) and 10(-7) M, respectively. However, AA560 nearly completely blocked cell growth at 10(-5) M. At a 2 mg daily dose for 13 days, (1) and AA560 powerfully inhibited tumor growth in castrated DS mice treated with testosterone propionate but oxendolone had almost no effect. Anthrasteroids and oxendolone showed weak but significant agonistic activity in vivo. Anthrasteroids markedly inhibited 5 alpha-reductase activity of SC115, oxendolone weakly and AA560 not at all. The remarkable antiandrogenic activities of (1) and AA560 may partially result from their higher affinities for the AR of SC115 but other yet unknown mechanisms may also contribute to these activities.

5-alpha Reductase Inhibitors↗
PubMed1990

Intracellular responses from UV-sensitive cells in the photosensory pineal organ.

A new type of cell having high sensitivity in the ultraviolet (UV) range was found in the pineal organ of the river lamprey. Lampetra japonica, by intracellular recordings. This UV-sensitive cell responded to light with graded hyperpolarizations and had the maximum sensitivity at 380 nm. The response of the cell was much slower than that of the usual pineal photoreceptor with the peak spectral sensitivity at 525 nm. Intracellular injection of Lucifer yellow revealed that the cell consists of 3 parts, corresponding to an outer segment, an inner segment and a terminal of photoreceptor cell. The apical part of the cell protruded into the lumen and the inner segment situated in the layer of photoreceptor cells. It was concluded that this UV-sensitive cell was a UV-specific receptor cell.

Animals↗
PubMed1990

Site-specific oxidation of angiotensin I by copper(II) and L-ascorbate: conversion of histidine residues to 2-imidazolones.

The reaction of a histidine-containing peptide (angiotensin I) with copper (II)/ascorbate under physiological conditions has been studied chemically. In the presence of a catalytic amount of copper(II) ion, ascorbate mediated the oxidative damage to the peptide via selective loss of the histidine residue. Furthermore, the reaction of copper(II)/ascorbate with the peptide gave two products (AGT-1 and AGT-2) selectively. From amino acid analysis of the modified peptides, it was found that either of the two histidine residues within the native peptide was modified. Amino-terminal sequence analysis indicated that AGT-1 and AGT-2 were modified at the His9 and the His6, respectively. In addition, the data of FAB-MS and 1H NMR suggested that the unknown residues (modified histidine) within AGT-1 and AGT-2 should have the 2-imidazolone structure. In order to confirm the 2-imidazolone residue in both modified peptides, they were hydrolyzed and analyzed by reverse-phase HPLC. The result demonstrated that the acid hydrolysis of modified peptides gave a product which was identical to authentic 2-imidazolone residue. Consequently, it was confirmed that the reaction of Cu(II)/ascorbate occurs specifically at the C-2 position of the imidazole ring of the histidine residue within a peptide.

Amino Acid Sequence↗
PubMed1990

Direct inhibition of smooth muscle myosin light chain kinase by arachidonic acid in a purified system.

The direct effect of arachidonic acid (AA) on the phosphorylation of smooth muscle myosin light chain (SMLC) by smooth muscle myosin light chain kinase (SMLCK) was assessed in a purified system. AA inhibited the phosphorylation of SMLC by SMLCK in a dose dependent manner. Increasing the amount of calmodulin (59 nM and 590 nM) did not reverse this inhibition. Linoleic acid and oleic acid also inhibited the phosphorylation. The inhibitory potency of these unsaturated fatty acids paralleled the number of cis double bonds. These results show that SMLCK is directly inhibited by unsaturated fatty acids including AA.

Animals↗
PubMed1990

Immunochemical detection of human blood in feces.

We have developed a new immunochemical test for fecal occult blood utilizing enzyme-linked immunosorbent assay (ELISA) of human hemoglobin (HbAo) and transferrin (Tf) simultaneously. The ELISA had a sensitivity of about 15 ng/ml Hb, and the measurable range was 1.5-750 micrograms Hb per g feces. The stability of Tf in feces was greater than that of Hb. In 17 out of 18 patients with colon cancer, 8 out of 15 patients with colon polyps, and 11 out of 20 patients with upper-gastrointestinal disorders. The Hb and Tf values were more than 10 micrograms/g feces, in terms of Hb concentration. The ELISA for human fecal HbAo and Tf might be useful for the diagnosis of gastrointestinal disorders.

Animals↗
PubMed1990

S-phase fraction of human prostate adenocarcinoma studied with in vivo bromodeoxyuridine labeling.

Forty-six patients with adenocarcinoma of the prostate were given an intravenous infusion of the thymidine analogue, bromodeoxyuridine (BrdU), 200 mg/m2, at the time of needle biopsy or transurethral resection to label tumor cells in the DNA synthesis phase. The tumor specimens were stained by an indirect immunoperoxidase method with anti-BrdU monoclonal antibody. The BrdU labeling index, S-phase fraction, was determined by counting the number of BrdU-labeled cells in the tissue sections. S-phase fraction correlates with the results of histologic tumor grade, Gleason score, and growth patterns. The higher S-phase fraction may indicate biologic malignancy. Moreover, the degree of heterogeneity concerning S-phase fraction distribution within prostate cancer tissue could be evaluated and the findings compared with the morphologic appearance. The authors results suggest that the measurement of BrdU labeling index in prostate cancer may prove to be a new objective and quantitative assay for biologic potential of individual tumors.

Adenocarcinoma↗
PubMed1990

Highly site-specific oxygenation of 1-methylhistidine and its analogue with a copper (II)/ascorbate-dependent redox system.

The reaction of histidine-related materials with copper(II) and ascorbate under physiological conditions has been studied chemically. We discovered that 1-methylimidazole and its analogues, including biological metabolites L-1-methylhistidine and anserine (beta-alanyl-L-1-methylhistidine), exhibited dramatic reactivity with copper(II)/ascorbate. Reaction of copper(II) and ascorbate occurs specifically at the C-2 position of the imidazole ring of L-1-methylhistidine and anserine derivatives with mono-oxygenation to give the 1-methyl-2-imidazolones in good to excellent yields (70-80%). The occurrence of an oxocopper(III) intermediate in the oxidation process of ascorbate is postulated.

Acetylation↗
PubMed1990

Hypercoagulability in acute ischemic stroke: analysis of the extrinsic coagulation reactions in plasma by a highly sensitive automated method.

The coagulability of plasmas from 63 patients with acute ischemic stroke (cerebral thrombosis and cerebral embolism) was analyzed by an automated method for prothrombin time using a fluorogenic peptide substrate. The fluorogenic prothrombin time (FPT) of patients' plasmas collected within 48 hr after onset, as expressed as percent of control plasma, was significantly higher in cerebral thrombosis than in an age-matched control group (p less than 0.01). The high values of FPT in cerebral thrombosis patients were observed until the 30th day after onset. On the other hand, FPT values in cerebral embolism patients were not significantly different than that of the control group. Factor VII activity levels in cerebral thrombosis patients were significantly higher than those of the control group and cerebral embolism patients, while levels of factor X activity were not significantly different among these groups. Although FPT and factor VII activity in these stroke patients did not significantly correlate, factor VII activity did correlate well with factor VII antigen. Decreased levels of antithrombin III and elevated levels of FDP and alpha 2-antiplasmin-plasmin complexes were observed only in cerebral embolism patients. Our findings strongly suggest that patients with cerebral thrombosis have been in a hypercoagulable state before the onset of symptoms, which was caused in part by an increase of factor VII activity/antigen, and in part by other unknown mechanisms. In contrast, patients with cerebral embolism were in a low grade consumptive coagulopathy.

Adult↗
PubMed1990

A novel mechanism for oxidative cleavage of prolyl peptides induced by the hydroxyl radical.

Mechanism for the oxidative cleavage of proline-containing peptides induced by the hydroxyl radical (.OH) has been studied. Accompanying the oxidation of prolyl peptides, we discovered the formation of significant amounts of gamma-aminobutyric acid (GABA) in the acid hydrolysates of the oxidized peptides. GABA was assumed to be derived from the 2-pyrrolidone compound and, in addition, its generation led to the assumption that prolyl peptides were mainly cleaved at the proline residues by .OH, accompanied by the oxidative modification of proline by itself. Hence, in order to confirm this prediction, we undertook the reaction of proline with .OH using proline analogue (Z-proline) and isolated the 2-pyrrolidone compound as the major product. We proposed a novel mechanism for formation of the 2-pyrrolidone compound induced by .OH, which has been established for the first time in the oxidative cleavage of prolyl peptides.

Collagen↗