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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 523 records · Page 29Linked to original sources

Specific immunotherapy reduces the antigen-dependent production of eosinophil chemotactic activity from mononuclear cells in patients with atopic asthma.

BACKGROUND: The efficacy of specific immunotherapy has been verified. There is accumulating evidence focusing on the T lymphocyte-eosinophil interaction in the pathogenesis of asthma. The aim of this study was to clarify whether immunotherapy affects the production of eosinophil chemotactic activity (ECA) from peripheral blood mononuclear cells (PBMC). METHODS: PBMC obtained from persons with bronchial asthma who were sensitive to Dermatophagoides farinae (Df) or from healthy volunteers were cultured for 96 hours in the presence or absence of Df. ECA in culture supernatants was assayed by means of the modified Boyden's chamber method. RESULTS: There was no significant difference in the baseline levels of ECA between asthmatic persons treated with immunotherapy and those without immunotherapy. The addition of Df (10 to 10(4) ng/ml) enhanced the ECA production in a dose-dependent fashion in asthmatic persons without immunotherapy, and there was a statistically significant correlation between the concentrations of Df and the levels of ECA (rk = 0.34; p < 0.05). In contrast, Df-dependent ECA production was suppressed in asthmatic persons with immunotherapy, and the suppressive effect was observed from 4 weeks after rush immunotherapy. CONCLUSIONS: These results indicate that immunotherapy induces the suppression of antigen-dependent production of ECA from PBMC. This may contribute to the attenuation of eosinophil infiltration into the airways in asthma patients.

Adolescent↗

Detection of interleukin-5 messenger RNA and interleukin-5 protein in bronchial biopsies from asthma by nonradioactive in situ hybridization and immunohistochemistry.

Recently direct evidence for the role of interleukin-5 (IL-5) in eosinophilic inflammation in the airways of persons with asthma has been provided by an in situ hybridization study that used radioisotope-labeled IL-5 complementary RNA probes. Radioisotope-labeled probes, although sensitive, require autoradiographic detection, which is time-consuming. In the most recent study we attempted to detect IL-5 messenger RNA in the bronchial biopsy specimens from patients with asthma using nonradioactive in situ hybridization, which gives rapid results. Bronchial biopsy specimens were obtained from eight patients with asthma and seven diseased control subjects. IL-5 complementary DNA probes were labeled with digoxigenin-deoxyuridine triphosphate and hybridized to permeabilized sections. Hybridization signals were visualized by an immunohistochemistry technique. Positive hybridization signals were observed in six of the eight biopsy specimens from patients with asthma. Pretreatment with ribonuclease or hybridization with an unrelated probe produced negative results. Immunohistochemical staining of serial sections with a monoclonal antibody to IL-5 revealed that a few cells within the mucosa positively stained, suggesting active synthesis of IL-5. Biopsy results from the seven diseased control subjects did not show any hybridization signal. These results confirm and extend previous observations of IL-5 messenger RNA expression in the airways of patients with asthma, and suggest that digoxigenin-labeled IL-5 complementary DNA probes would be a powerful research tool.

Adult↗

Leukemic cell membrane from acute myelogenous leukemias with massive mast cell infiltration has a mast cell differentiation activity under culture condition containing interleukin 3.

Five cases of acute myelogenous leukemia with massive mast cell infiltration in bone marrow and leukemic tumors of the soft tissue were examined to elucidate the relationship between leukemic cells and mast cells. Leukemic cells in each case showed no basophil/mast cell features and differentiated to neutrophil-like cells in liquid culture. Isolated mast cells failed to proliferate with or without growth factors used irrespective of culture conditions. Mononuclear cell fraction obtained from all patients gave rise to relatively numerous mast cells in interphase culture using IL-3 but not in other culture systems. The simultaneous addition of leukemic cell membrane and IL-3 or delayed addition of leukemic cell membrane produced more numerous and mature mast cells in the upper layer of interphase culture using IL-3. However, addition of leukemic cell membrane alone failed to increase the number of mast cells. Similar results were obtain using mononuclear cells obtained from volunteers and cord blood cells. These results indicate that a cell to cell contact or interstitial substance together with IL-3 are essential requirements for growth and maturation of mast cell precursors and that the cell membrane itself in some cases of leukemia has the ability to induce maturation of mast cell precursors.

Adolescent↗

Characterization of newly established adriamycin resistant human leukemic cell lines (KY-ADR1 and KY-ADR2).

New adriamycin (ADR) resistant human leukemic cell lines (KY-ADR1 and KY-ADR2) have been established. KY-ADR1 was selected from a cytosine arabinoside (Ara C) resistant cell line by gradually increasing the concentration of ADR and KY-ADR2 from the parental cell line, KY-821, by the same method. The IC50s of both cell lines were 4.3 x 10(-5) and 3.6 x 10(-5) M ADR, respectively. Both lines revealed a similar cross resistance to various anticancer drugs, but KY-ADR1 was resistant to Ara C, whereas KY-ADR2 was sensitive. MDR1 gene was over-expressed and P-glycoprotein was expressed on the cytoplasmic membrane in both lines. Neither verapamil nor cyclosporin A could completely reverse ADR resistance. In addition, no significant changes in topoisomerase II and glutathione-s-transferase levels were detected. These findings indicate that ADR resistance in both cell lines is mainly mediated by P-glycoprotein and some other mechanism may be present. Interestingly, growth of both cell lines was stimulated by natural IL-1 and not affected by TNF alpha and IFN gamma, whereas growth of parental KY-821 was inhibited by these factors. These cell lines will provide new biological aspects on drug resistant leukemic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effects of dietary restriction on induction of unscheduled DNA synthesis (UDS) and replicative DNA synthesis (RDS) in rat liver.

The effects of dietary restriction on the induction of unscheduled DNA synthesis (UDS) and replicative DNA synthesis (RDS) were studied in the hepatocytes of F344 rats exposed in vivo to dimethylnitrosamine (DMN) or CCl4. The animals were given food ad libitum, a restricted amount of food (4 g/rat/overnight) or no food. Hepatocytes were isolated 2 h after oral administration of DMN at a dose of 5 mg/kg body weight and 48 h after oral administration of CCl4 at a dose of 400 mg/kg body weight, and incubated for 4 h in Williams' medium E supplemented with either [3H]thymidine for UDS or 5-bromodeoxyuridine for RDS. UDS was determined by autoradiography and RDS was determined by the immunoenzymatic staining method. The background levels of UDS (net grains/nucleus) and RDS (cells in S phase) in control were -12.4 and 0.64% for ad libitum feeding, -6.8 and 0.04% for restricted feeding, and -8.1 and 0% for fasting. UDS induced by DMN and RDS induced by CCl4 were 19.4 and 3.3% for ad libitum feeding, 34.5 and 10.4% for restricted feeding, and 47.8 and 15.1% for fasting. DMN demethylase activity in rat liver was also found to increase with dietary restriction. These results indicate that dietary restriction modulates the responses of UDS and RDS in the liver of rats.

Animals↗

Atypical appearance of adrenal pseudocysts.

We report 2 cases of adrenal pseudocysts that resulted from hemorrhage into a normal adrenal gland and that showed atypical imaging features on computerized tomography and ultrasonography. The presence of a solid component within the mass and/or central calcification, which is unlike the typical features of adrenal pseudocyst, suggested a diagnosis of adrenal tumor. The solid component diminished on computerized tomography in 26 days in case 1 and in 16 days in case 2, which seemed to represent resolving hematoma. The atypical appearance of these adrenal pseudocysts, especially the changeable pattern of the solid component within the mass, should be kept in mind to ensure a correct preoperative diagnosis.

Adrenal Gland Diseases↗

Different mechanisms of regioselection of fatty acid hydroxylation by laurate (omega-1)-hydroxylating P450s, P450 2C2 and P450 2E1.

P450 2C2 as well as P450 2E1 [Fukuda, T. et al. (1993) J. Biochem. 113, 7-12] catalyzed the hydroxylation of medium chain fatty acids, although the regioselectivity of substrates of the former contrasted with that of the latter. Whereas P450 2E1 hydroxylated C9-C18 fatty acids at the omega-1 position and to a much lesser extent at the omega and omega-2 positions, P450 2C2 hydroxylated C9-C13 fatty acids at different positions dependent on the chain length of fatty acids. Among the fatty acids used as the substrate, undecanoate was hydroxylated at the omega-1 position almost exclusively by P450 2C2. The proportion of omega-hydroxylated products produced by P450 2C2 was markedly increased with decreasing chain length of fatty acids, while the hydroxylation positions were enlarged to the omega-3 position with tridecanoate. When the conserved Thr at the putative distal helix was replaced with Ser, the substrate regioselectivity of the two P450s was affected in different manners. The mutation of P450 2C2 did not change the hydroxylation positions of C9-C12 fatty acids, but caused a significant decrease in the proportion of the omega-1 hydroxy analog in the total products. In sharp contrast to P450 2C2, the mutated P450 2E1 gave additional products to those with the wild-type P450, and the number of different products increased with increasing chain length of the fatty acids. Thus, the products of palmitate hydroxylation were identified as omega-1, omega-2, omega-3, omega-4, omega-5, omega-6, and omega-7 monohydroxy isomers using gas chromatography-electron impact mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Human parathyroid hormone: efficient synthesis in Escherichia coli using a synthetic gene, purification and characterization.

Human parathyroid hormone is a peptide hormone consisting of 84 amino acid residues. Production of small proteins by direct expression in Escherichia coli is often unsuccessful owing to susceptibility of the mRNA and/or the product to endogenous enzymes. In this study, direct expression of the hormone at an excellent level (over 100 mg/L) has been achieved by using a suitably designed synthetic gene under the control of the T7 promoter. The protein produced in bacteria was extracted and easily purified in a good yield of 27 mg/L. The purified product was physico-chemically identified as intact human parathyroid hormone from the results of amino acid analysis, N-terminal sequencing, and peptide mapping using fast atom bombardment mass spectrometry. In biological assays the purified product stimulated adenylate cyclase in vitro, promoted bone growth and increased the serum osteocalcin in rats to the same extent as the authentic hormone.

Amino Acid Sequence↗

Peripheral carcinoid tumor of the lung with focal melanin production.

A case of carcinoid tumor of the lung with focal melanin production was encountered in a 56 year old Japanese woman. The tumor was found 16 years previously by mass survey chest X-ray and had enlarged two-fold in the intervening period. The tumor consisted of a variety of tumor cells showing a spindle, polygonal and pleomorphic appearance with abundant vasculature in the stroma. All tumor cells showed argyrophilia, together with a few showing argentaffinity. Melanin-containing tumor cells were also present in parts. Ultrastructurally, most tumor cells possessed various numbers of neurosecretory granules and a few of them contained granular type melanosomes. Tumor cells were connected with desmosomes and a few of them contained tonofilament-like microfilaments. Only a few contained both neurosecretory granules and melanin. By immunohistochemistry, serotonin, met-enkephalin and beta-endorphin positive cells were observed scattered throughout the tumor. A few tumor cells positive for tyrosine hydroxylase were also detected. Additionally, most tumor cells were positive for keratin. On the basis of these findings, the tumor of the current case is a pulmonary carcinoid tumor with focal melanin production.

Carcinoid Tumor↗

The colonic neobladder: a stoma-free bladder substitute after radical cystectomy--preliminary results in six patients.

We have used a urethral colonic pouch for total bladder replacement in 6 bladder cancer patients after radical cystectomy. The distal ileum, cecum, ascending colon and the right third of the transverse colon were isolated. The cecum and colon were opened along the tenia and a detubulized pouch was created. The ureters were sutured to the terminal ileum. The maximum pressure wave measured ranged 22-58 cmH2O, and the amount of residual urine varied between 0 and 58 ml. All patients were completely continent during the day and slight incontinence at night was observed in 3. By amputating the right colonic artery, the pouch is easily moved to the urethral stump and serves as a low pressure neobladder after cystoprostatectomy.

Adult↗

Anti-bacterial antibodies in Epstein-Barr virus (EBV)-transformed oligoclonal B-cell lines established from normal persons and autoimmune disease patients.

We have established 950 and 430 oligoclonal B-lymphoblastoid cell lines (LCL) from two normal persons and eight autoimmune disease patients, respectively by using Epstein-Barr virus (EBV)-induced transformation. To re-evaluate the EBV technique for production of human monoclonal antibodies (mAb) related to infectious disease, we screened these oligoclonal LCLs for antibodies against 31 bacterial strains systematically. A total of 74 cultures out of 1380 were reactive to a total of 18 strains out of 31. Among these, eight cultures showed 10(-3) antibody (Ab) titers to Pseudomonas aeruginosa serotypes C, E, F and I, Staphylococcus aureus, Serratia marcescens and Bacillus cereus. Ten cultures showed 10(-2) Ab titers to Ps. aeruginosa serotypes D, E, F and I, Ps. maltophilia, Staph. epidermidis, Klebsiella ozaenae, Ser. marcescens and B. subtilis. The results reveal the further possibilities for the EBV technique to produce various infectious disease-related human mAbs.

Adolescent↗

The pharmacological properties of Y-23684, a benzodiazepine receptor partial agonist.

1. The pharmacological properties of a benzodiazepine receptor (BZR) partial agonist, Y-23684 were investigated in comparison with those of diazepam, a conventional BZR full agonist. 2. Y-23684 and diazepam showed high and selective affinity for the BZR with Ki values of 41 and 5.8 nM, respectively. 3. In contrast to diazepam, variability was noted in the anticonvulsive potency of Y-23684 depending on convulsants (bicuculline, pentylenetetrazol and maximal electrical shock). Y-23684 produced the most potent protective effect against bicuculline in rats and mice with ED50S of 1.3 and 1.2 mg kg-1, respectively. 4. In rat conflict models (Geller-Seifter and water-lick tests), Y-23684 produced an antipunishment action at doses 2-4 times lower than diazepam. In contrast to diazepam, Y-23684 did not affect unpunished responding up to 50 mg kg-1 in the Geller-Seifter test. 5. In other rat models of anxiety (social interaction and elevated plus-maze tests), Y-23684 was as efficacious as and ten fold more potent than diazepam. In a mouse model of anxiety (exploration (light/dark box) test), Y-23684 was as efficacious and two fold less potent as diazepam. In these paradigms, Y-23684 showed a selective anxiolytic profile over a wide dose-range without loss of efficacy and sedative action. 6. The impairment of motor coordination (rotarod) and potentiation of CNS depressants (ethanol and hexobarbitone) by Y-23684 was much weaker than that of diazepam. 7. These results suggest that Y-23684 would be a potent and selective anxiolytic agent in man with less side-effects than conventional BZ-anxiolytics.

Animals↗

Predominance of myeloid antigens in CD34-positive peripheral blood stem cells over those in bone marrow after administration of granulocyte colony-stimulating factor.

We analyzed the surface phenotype of CD34-positive (CD34+) cells in peripheral blood (PB) during the period of hematopoietic recovery following myelosuppressive chemotherapy. A significantly higher proportion of PB CD34+ cells coexpressed the CD13 and CD33 myeloid antigens (80.8%, 78.1%, respectively) than did BM CD34+ cells (45.8%, 37.8%, respectively) (both p < 0.01). In particular, the CD13 positivity of PB CD34+ cells harvested with granulocyte colony-stimulating factor (G-CSF) was significantly higher than that of those without G-CSF. Most of the PB CD34+ cells possessed the HLA-DR antigen, and less than 10% of the CD34+ cells coexpressed a mature cell antigen, such as CD14, GPA or Plt-1. The administration of G-CSF enhanced the appearance of significantly larger amounts of CD13+ 34+ and CD33+ 34+ cells (both p < 0.01). This G-CSF mobilization also resulted in an increased number of CD13- 34+ and CD33- 34+ cells and all types of colony-forming cells. On the other hand, macrophage colony-stimulating factor administration exerted little influence on the mobilization of PB CD34+ cells. Thus, G-CSF seemed to induce not only an expansion of circulating hematopoietic stem cells but also the myeloid differentiation of stem cells.

Adolescent↗

[Enterococcus faecium obtained from surveillance cultures of the stool of the patients with hematological malignancies].

Surveillance cultures of the stool were obtained from 55 patients with hematological malignancies, who have been receiving norfloxacin or tosufloxacin during their neutropenic periods, from May, 1991 to September, 1992. Cultures were performed using 5% blood agar with piperacillin 300 micrograms/ml and amikacin 20 micrograms/ml and bacteria resistant to these antibiotics were analyzed further. Thirty-four over 55 patients were positive for enterococci and 22 strains of 23 examined were Enterococcus faecium. They are resistant to quinolones, aminoglycosides, cephalosporins and penicillins but not to vancomycin. Eighteen of them were also resistant to high-dose gentamicin. Appropriate measures should be used to prevent intrahospital spread of these resistant isolates.

4-Quinolones↗

Aortic dissection caused by angiographic procedures.

PURPOSE: To describe findings in, and the clinical course and outcome of, aortic dissection (dissecting aneurysm) caused by angiographic procedures. MATERIALS AND METHODS: The records of approximately 15,500 angiographic procedures performed between 1985 and 1991 were reviewed. In the six cases of iatrogenic aortic dissection identified, computed tomography (CT) was performed for diagnosis, follow-up, or both. RESULTS: The type of aortic dissection was Stanford type A in three patients and Stanford type B in three patients. The sites of injury were the abdominal aorta (n = 2), right brachiocephalic artery (n = 2), middle of the thoracic aorta (n = 1), and right common iliac artery (n = 1). One patient had anterograde dissection from the site of injury; two patients, retrograde dissection; and three patients, extensive dissection that extended in both anterograde and retrograde directions. Retrograde dissections decreased in size or disappeared in 1-3 months due to the absence of reentry, whereas anterograde dissections persisted during follow-up (15-27 months). All patient were treated without surgery. CONCLUSION: Angiographers should be aware of this potentially serious complication. The extent and type of the aortic dissection can be determined with CT.

Aged↗

Multiple intrahepatic aneurysms following transcatheter arterial embolization. Work in progress.

PURPOSE: To discuss the mechanism of multiple intrahepatic aneurysm formation after transcatheter arterial embolization (TAE) performed in five patients with hepatocellular carcinoma. MATERIALS AND METHODS: TAE was performed with gelatin sponge particles and iodized oil as embolic materials. Mitomycin C was also used in four cases. RESULTS: Three to 14 aneurysms 1-6 mm in diameter were found in third-to sixth-order branches of the hepatic arteries at repeat angiography performed 25-45 days after TAE. Follow-up angiograms in three cases revealed that most aneurysms were no longer apparent except in one patient in whom two aneurysms remained and were larger than before. In none of the five cases were any signs of aneurysm rupture noted. CONCLUSION: Radiologists should be aware of this complication of TAE. It is speculated that the main cause of aneurysm formation in these patients was the embolic agents used.

Aneurysm↗

Intravascular ultrasound of coronary arteries in children. Assessment of the wall morphology and the lumen after Kawasaki disease.

BACKGROUND: The long-term clinical issue in Kawasaki disease (KD) concerns the coronary artery lesion. Two-dimensional echocardiography and coronary angiography are routine examinations to evaluate the coronary lesions; however, these are not adequate to assess the wall morphology of the coronary artery (CA). Intravascular ultrasound imaging (IVUS), a new technology for the evaluation of the coronary artery lumen and wall morphology in vivo, was performed for patients after KD in their long-term follow-up, and we examined the new insights it gave. METHODS AND RESULTS: IVUS was performed during cardiac catheterization in 20 subjects (10 patients after KD who still had coronary aneurysms or regressed coronary aneurysms, 2 after KD who had no coronary abnormal lesion, and 8 control patients with congenital heart disease and normal CA). We evaluated the wall structure at 10 to 15 sites of the CA in each patient. IVUS was performed with a commercially available ultrasound imaging catheter. Four sites of a CA aneurysm in KD demonstrated a markedly dilated lumen without thickened intima. One site of a CA aneurysm with calcification demonstrated an asymmetrical lumen by a dense echo with acoustic shadows. Twenty-two sites of a regressed CA aneurysm demonstrated a marked symmetrical or asymmetrical thickening of the intima with a dense echo, in which the size of the lumen was similar to that at a site near a regressed aneurysm. The sites of angiographically normal CA revealed normal structures and a thin intima in many instances. Nine of 28 sites in KD with a CA abnormal lesion, particularly near a coronary aneurysm or regressed aneurysm, demonstrated a mild thickening of the intima. All the 10 sites in KD without a CA abnormal lesion and all the 25 sites in patients with congenital heart disease with normal CA demonstrated a smooth intima. CONCLUSIONS: This study demonstrated that the site of a regressed coronary aneurysm has a markedly thickened but smooth intima. The sites of angiographically normal CA after KD with or without a coronary lesion demonstrated normal IVUS findings in most instances but in some cases revealed a mild intimal thickening. IVUS is useful to evaluate the CA wall morphology and may contribute to the assessment of long-term CA sequelae and the possible development of arteriosclerotic changes in KD.

Adolescent↗