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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 901 records · Page 50Linked to original sources

Effects of twenty-three drugs on the metabolism of FK506 by human liver microsomes.

We investigated the effects of 23 drugs on the metabolism of FK506 by human liver microsomes. Acyclovir, amphotericin B, cefixime, cefotaxime, ciprofloxacin, cyclosporin A, diltiazem, enoxacin, erythromycin, ethinyl estradiol, fluconazole, fosfomycin, kanamycin, lincomycin, loxoprofen, minocyclin, nifedipine, nilvadipine, norethindrone, ofloxacin, phenobarbital, prednisolone, or rifampicin was added to the reaction media at equimolar or at ten times an excess molar ratio of the substrate concentration; their effects on FK506 metabolism were examined. Drugs known to be the substrate of cytochrome P-450 3A inhibited the metabolism of FK506, and among the drugs tested, the inhibition by cyclosporin A and nifedipine was the strongest.

Anti-Infective Agents↗

Immunoreactive-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa in patients with nonulcer dyspepsia and peptic ulcer disease.

Changes in immunoreactive (ir)-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa were examined in subjects with nonulcer dyspepsia (NUD) and peptic ulcer to clarify the relationship between these peptides and dyspeptic symptoms. Fifty-six patients with NUD were divided into two subject subgroups as follows: 22 patients with upper abdominal discomfort, nausea, and/or vomiting (motility disorder group) and 34 patients complaining of upper abdominal pain [ulcer-like disorder (UD) group]. These patients were compared with either an age- and sex-matched group of asymptomatic outpatients without any organic disease (control group: n = 51), or to a group with peptic ulcer (PU group: n = 30). Ir-somatostatin concentrations of the gastric mucosa were significantly higher in UD group than in PU, motility disorder, or control group, and ir-substance P concentrations in the UD group were higher than in the PU group. No difference in ir-calcitonin gene-related peptide concentrations was observed among the four groups. These results indicate that there may be two distinct subgroups in NUD, and that NUD is not just a stage within the spectrum of peptic ulcer disease from the viewpoint of several gastrointestinal-hormone concentrations of the human gastric mucosa.

Biopsy↗

Autoradiographic analysis of the uptake of [3H]dopamine, [3H]angiotensin II and [3H]gamma aminobutyric acid by the chicken thrombocyte.

The ability of chicken thrombocytes to take up and store transmitters of different categories, such as dopamine, angiotensin II and gamma aminobutyric acid (GABA), was examined by electron microscope autoradiography. Chicken thrombocytes selectively took up [3H]dopamine, which was stored in large vacuoles with peripherally situated electron-dense granules. Exogenous [3H]angiotensin II was also taken up by chicken thrombocytes. This accumulated in the same large vacuoles in which [3H]dopamine was stored. No active uptake of exogenous [3H]GABA was detected. The results indicate that chicken thrombocytes take up exogenous dopamine and angiotensin II which both appear to be stored in the same vacuoles, the amine storage organelles.

Angiotensin II↗

The role of novel 30-kD protein in human podocytes: special relevance to proteinuria in glomerulonephritis.

A new monoclonal antibody (MAb) was raised against human glomerular components to investigate the possible existence of glomerular antigens reflecting cellular adaptation in glomerulonephritis. The MAb recognized a podocyte antigen as well as those expressed on renal arterial endothelial cells and smooth muscle cells by indirect immunofluorescence. An additional, but weaker immunoreaction was found in epithelial cells of the Bowman's capsule. This MAb recognized a 30-kD protein on western blotting of glomerular extracts under non-reducing and reducing conditions. Immunoperoxidase electron microscopy revealed that this antigen is present within the cytoplasm, but not on the cell membrane of the podocytes. Moreover, the antigen was found to be reduced in the glomeruli of patients with minimal change glomerulonephritis. These results suggest that the 30-kD protein is a novel protein, which we hypothesize is involved in maintenance of the structural and functional integrity of the podocytes. In addition, reduced expression of the 30-kD protein in the podocytes may be related to the increasing proteinuria in minimal change glomerulonephritis.

Epithelium↗

[In vitro susceptibility to fluconazole of fungal strains freshly isolated from child patients with deep-seated mycoses].

The susceptibility to fluconazole (FLCZ) were evaluated for 40 strains of 8 yeast species and 4 strains of 3 Aspergillus species, all of which were isolated from clinical specimens during clinical trials of FLCZ in child patients performed from January 1991 to January 1993 in this country. The in vitro activity of FLCZ against yeast isolates and Aspergillus isolates were measured using the microdilution method with semisolid SAAMF (synthetic amino acid medium fungal) agar and the macrodilution method with Eagle MEM (minimum essential medium), respectively, using amphotericin B (AMPH) and flucytosine as the reference drugs. Out of all yeast species tested, Candida albicans and Candida tropicalis were the most susceptible to FLCZ with geometric mean (GM)-MICs of < 0.4 microgram/ml that were far less than the corresponding values for AMPH or flucytosine. On the other hand, FLCZ showed the lowest activity against Candida krusei and Candida glabrata with GM-MICs of approximately 10 micrograms/ml that were slightly higher than those for AMPH. The susceptibilities to FLCZ of Candida parapsilosis, Candida pelliculosa (anamorph of Hansenula anomala), Candida famata, and Trichosporon cutaneum were intermediate. Antifungal activities of FLCZ and the 2 reference drugs against aspergilli were determined on the basis of the amount of total protein recovered from drug-treated cultures relative to that from drug-free control cultures. Fifty percent and 90% inhibitory concentrations of FLCZ against 2 isolates of Aspergillus fumigatus were 6.25-25 micrograms/ml and 50 micrograms/ml, respectively. Against this and 2 other species of Aspergillus, AMPH appeared more highly active than FLCZ.

Amphotericin B↗

[A case of acute eosinophilic pneumonia with Kerley's lines (A and B) on chest X-ray].

A 18-year-old woman presented to our hospital complaining of an acute onset of progressive dyspnea with nonproductive cough and high fever. The patient was in her usual good health until the previous day, when she started to develop symptoms 8 hours after taking aspirin for a headache. The chest roentgenogram revealed Kerley's lines (A and B), perivascular cuffing and hilar haze with bilateral pleural effusions. Body temperature was 38 degrees C and PaO2 was 48 torr. Infectious diseases and extrinsic allergic alveolitis were excluded. The lymphocyte stimulating test was negative for aspirin. Acute eosinophilic pneumonia was strongly suggested by bronchoalveolar lavage showing a marked increase in eosinophils without peripheral eosinophilia. By the seventh hospital day all clinical and radiographic signs were improved without steroid therapy. Most cases of acute eosinophilic pneumonia reported previously showed diffuse infiltrative shadows on the chest roentgenogram. The present case had interesting radiographic findings which suggested interstitial pulmonary edema.

Acute Disease↗

[Therapeutic efficacies of neticonazole (SS717) cream and solution in experimental cutaneous Candida albicans infection of guinea pigs].

The therapeutic efficacies of 1% neticonazole (SS717) cream and solution on experimental cutaneous Candida albicans infection produced in prednisolone-treated guinea pigs were compared with those of 1% bifonazole (BFZ). Active preparations or blank vehicles were applied once daily for 3 consecutive days starting 5 days postinfection. Therapeutic effects were assessed on the basis of viable counts recovered from the infected loci 9 days postinfection. In animals treated with SS 717 or BFZ cream, a significant mycological improvement was observed when compared to untreated controls. A significant therapeutic efficacy of a SS717 cream compared to cream vehicle was also noted, while there was no significant difference in the recovery of Candida between the untreated control group and the cream vehicle-treated groups. The mycological result of the SS717 solution treated group was significantly superior to those of the untreated control group, the solution vehicle-treated group and the BFZ solution-treated group. The treatment with a solution vehicle or a BFZ solution appeared to lower, though not to a significant level, viable counts at the infected loci. These results led us to the conclusion that both SS717 cream and solution preparations exhibited significantly superior activity to that of BFZ in experimental cutaneous candidasis of guinea pigs.

Animals↗

[In vitro antifungal activity of omoconazole nitrate, a new imidazole antimycotic].

In vitro antifungal activities of omoconazole nitrate (OMZ), a new topical imidazole antifungal agent, were studied against 364 strains of 22 genera and 47 species of stock cultures of a wide range of medically important fungi. The test was carried out using the agar dilution method with bifonazole (BFZ) as the reference drug. OMZ exhibited a broad spectrum of antifungal activities. Most of yeasts including Malassezia, dimorphic fungi, non-pigmented hyphomycetes and dermatophytes were almost equally or more greatly susceptible to OMZ than to BFZ, although the MIC values of these drugs against Candida and probably some other fungi were influenced differently by testing media. Comparable susceptibility to OMZ were observed for fresh clinical isolates of dermatophytes and Candida albicans. OMZ was also active against Malassezia. These results have encouraged us to proceed in vivo studies using animal models of cutaneous mycoses.

Antifungal Agents↗

[A basic study on a highly sensitive automated method for hypercoagulable state in plasma, fluorogenic prothrombin time (FPT) method].

A highly sensitive automated method, fluorogenic prothrombin time (FPT) method, was developed by a combination of a fluorogenic peptide substrate for thrombin and a centrifugal autoanalyzer (Cobas Bio). Using plasmas from stroke patients, we showed that the second reagent containing fluorogenic peptide substrate should be mixed after the first reagent containing tissue factor and plasma were mixed, that is, two steps method, in order to detect hypercoagulable state. When the first and the second reagent were mixed with plasma at the same time, that is, one step method, FPT was not sensitive to hypercoagulable state. We also showed that patient plasmas should be stored at -80 degrees C and subjected to FPT analysis immediately after thawing, not leaving at 4 degrees C or room temperature. Good correlation was observed on FPT of stroke patients using human tissue factor and bovine tissue factor. Another fluorogenic method was developed by the same principle for the evaluation of factors X and VII concentrations in plasma using deficient plasma of factor X or factor VII. Good correlation was observed on factors X and VII concentrations of stroke patients using human tissue factor and bovine tissue factor.

Blood Coagulation Tests↗

Characterization of the glomerular endothelial cell in culture.

Because of difficulties associated with the culture, cloning and propagation of glomerular endothelial cells (GENs), the biological properties of these cells remain largely unknown. We modified the methods established by Ballermann to propagate GENs from adult bovine kidney. We found that the addition of insulin, transferrin and selenium into the standard culture media was an important step in promoting the propagation of the first clone from a single cell and in maintaining the viability of the cells. These cells expressed factor VIII-related antigen and took up acetylated-LDL, but did not contain the Weibel-Palade body, unlike endothelial cells derived from large vessels. Furthermore, GENs were compared with aortic endothelial cells (AECs) to investigate the differences in culture conditions. Compared with AECs, GENs required a higher concentration of serum and the supplementation of growth factor to maintain their biological activity. In addition, GENs were very susceptible to trypsinization and produced prostaglandin E2 as a major cyclooxygenase product, whereas AECs produced PGI2. These findings suggest that GENs will be easily obtained from adult bovine kidney in culture and provide useful information on the functional properties of these cells under physiological and pathophysiological conditions.

Animals↗

[Structure of ADP-ribosylating enzyme and DNA repair].

ADP-ribosylation is a post-translational modification of protein using a respiratory coenzyme, NAD+, as a substrate. Poly(ADP-ribosyl)ation reaction in the nuclei has been thought to be involved in DNA repair. Cloning of poly(ADP-ribose)polymerase cDNA and gene has opened the way for analyzing the structure and functions of poly(ADP-ribose)polymerase at the molecular level. Poly(ADP-ribose)polymerase is a zinc-finger protein and binds to nicks of DNA. This enzyme is activated by binding to DNA and poly(ADP-ribosyl)ates nuclear proteins and poly(ADP-ribose)polymerase itself. Structural analysis of poly(ADP-ribose)polymerase from different classes has shown conserved motifs in the domain structures. In this review, recent advances in this field, including mono-ADP-ribosylation and cyclic ADP-ribose, are described.

ADP Ribose Transferases↗

[A case of an elderly SLE patient associated with acute renal failure].

It has been described that a rapid worsening in renal function is uncommon in the elderly patient with lupus nephritis. We report a case of a 76-year-old man with rapidly progressive lupus nephritis. On admission, laboratory studies revealed massive proteinuria, telescoped urine, thrombocytopenia and azotemia. Hypocomplementemia and the positive presence of anti-DNA antibody and lupus anticoagulant were also noted. Because of a rapid deterioration of renal function, he was started on a regimen of steroid pulse therapy and plasmapheresis. Serum levels of complements gradually increased after initiation of these treatments, and three weeks later, improvements of renal function and nephrotic syndrome were obtained. A renal biopsy specimen taken five months after admission showed diffuse membranous glomerulonephritis. In addition, we examined renal arterial blood flow with Doppler ultrasound, and significant improvements of the velocity and pulsatility were observed during recovery of the renal function.

Acute Kidney Injury↗

[The states of recovery of blood counts and serum ferritin levels after blood donation].

Complete blood counts and levels of ferritin in serum (S-Fer) in 62 college students were analyzed continuously to clarify the effects of blood donation. In 14 (45%) of 31 females, hemoglobin (Hb) and S-Fer levels showed decrease of more than 5% and 30%, respectively, four weeks after donation of 200ml or 400ml of blood. In 11 (35%) of the males and 6% of the females, Hb levels increased over 5% during the same period. In 61% of the males and 45% of the females, S-Fer levels decreased. In only 19% of the males, the Hb and S-Fer levels were unchanged. Red blood cell (RBC) counts and Hb levels showed almost the same pattern. In 39% of the males and 48% of the females, the white blood cell (WBC) counts decreased more than 10%. In 10% of the males and 23% of the females, WBC counts increased more than 10% after blood donation. The WBC and RBC counts did not always show the same pattern of variation. After blood donation, the incidence of iron deficiency anemia among females increased from 13% to 23% and the incidence of latent iron deficiency among females increased from 10% to 42%.

Adult↗

[The assessment of multiple coronary artery bypass with bilateral internal thoracic artery grafts].

From 1982 to March 1991, 68 patients underwent coronary artery bypass grafting (CABG) using bilateral internal thoracic arteries (ITA). There were 62 males (91.2%) and 6 females (8.8%) ranging from 33 to 74 years old (mean 58.5 +/- 9.2). Thirty four patients had old myocardial infarction (OMI) and left main trunk disease was seen in 8.5% of the patients. The number of grafts was 2 to 6 per patient with an average of 3.2 +/- 1.0. In bilateral ITA grafting the combinations of RITA to LAD and LITA to LCX were most frequently used. There were no operative deaths except for one death which occurred while at the hospital. The patency rates for the RITA and LITA were 98.3% and 96.7%, respectively. Postoperative complications included reexploration for bleeding and heart tamponade in 9 patients, and low output syndrome in 7 patients. The frequency of blood transfusion decreased with the use of cell saver. Routine bilateral ITA grafting for multiple CABG is considered safe, with the early patency being relatively better than with saphenous vein grafting.

Adult↗

Time course of plasma histamine and tryptase following food challenges in children with suspected food allergy.

This study was undertaken to investigate the kinetics of histamine and tryptase in the circulation of patients with food allergy and to determine whether the measurements of plasma histamine and tryptase concentrations after food challenges provided additional predictive markers for the diagnosis and evaluation of food allergy. Twenty-one open food challenges were performed on 13 patients with suspected food allergy. Plasma histamine and tryptase concentrations were measured during 4 hours after challenge. In the group of patients with immediate reactions after challenges, the mean plasma histamine concentration rose significantly at 120 and 240 minutes after the challenge, and the mean plasma tryptase concentration was increased significantly at 240 minutes after challenge. Plasma histamine and tryptase concentrations were measured during 24 hours after 8 open food challenges in 7 other patients with suspected food allergy. In each patient with a nonimmediate reaction, plasma histamine concentrations were increased at the onset of symptoms after challenge, but no plasma tryptase concentrations increased. The elevation of plasma histamine and tryptase in patients with immediate reactions following food challenge indicates mast cell activation. On the other hand, the elevation of plasma histamine without elevated plasma tryptase in the patients with nonimmediate reactions following food challenge may indicate basophil activation rather than mast cell activation. Plasma histamine and tryptase measurements after food challenge may be useful in the detection and evaluation of food allergy.

Adolescent↗

[Role of glomerular mesangial cells in the regulation of glomerular endothelial cell growth].

Because of difficulties of propagating and cultivating glomerular endothelial cells (GEN), the role of glomerular mesangial cells (GMC) in the regulation of GEN growth is still unknown. We cloned individually GEN and GMC from the same adult bovine kidneys, and a direct coculture system was established to examine the interactions between GEN and GMC. When cocultured with GMC which was growth arrested by mitomycin C, the GEN growth was inhibited by 63% after 8 days of the beginning of coculture. No inhibitory activity was detected when media conditioned by individual culture of GMC. In contrast, media conditioned by GEN cocultured with GMC inhibited bromodeoxyuridine (BrdU) uptake of GEN detected by flow cytometry. Addition of anti-transforming growth factor (TGF)-beta antibody to media conditioned by coculture blocked the inhibitory actions of conditioned media on GEN growth. Western blotting analysis of conditioned media by coculture revealed an existence of TGF-beta in the media. These results indicate that latent TGF-beta is produced by these cells and activated in coculture of GEN and GMC.

Animals↗