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Biomedical subjects

A Kondo

Publications and source records attributed to A Kondo.

At least 19 recordsLinked to original sources
PubMed2006

Ossifying fibroma of the mandible with primary hyperparathyroidism due to non-familial parathyroid adenoma.

Ossifying fibroma is an uncommon benign osteogenic neoplasm arising from cells of the periodontal ligament, typically with a slowly progressive enlargement of the affected bone. The neoplasm sometimes presents with hyperparathyroidism, most of which cases are due to familial parathyroid tumours. We report a rare case of ossifying fibroma of the mandible which showed very rapid growth and presented with primary hyperparathyroidism due to non-familial parathyroid adenoma. Despite improvement of parathyroid dysfunction after removal of the parathyroid adenoma, the tumour continued to grow very aggressively. The case required partial mandibular resection for complete resection of the tumour, and fixation of the remaining mandible with a titanium plate.

Adenoma↗
PubMed2006

Gene therapy of liver tumors with human liver-specific nanoparticles.

The development of safe and efficient liver-specific gene delivery approaches offers new perspectives for the treatment of liver disease, in particular, liver cancer. We evaluated the therapeutic potential of hepatotropic nanoparticles for gene therapy of liver tumor. These nanoparticles do not contain a viral genome and display the hepatitis B virus L antigen, which is essential to confer hepatic specificity. It has not been shown whether a therapeutic effect could be obtained using L nanoparticles in a human liver tumor xenograft model. Rats bearing human hepatic (NuE) and non-hepatic tumors were injected with L nanoparticles containing a green fluorescent protein (GFP) expression plasmid. GFP expression was observed only in NuE-derived tumors but not in the non-hepatic tumor. The potential for treatment of liver tumors was analyzed using L nanoparticles containing the herpes simplex virus thymidine kinase gene, in conjunction with ganciclovir pro-drug administration. The growth of NuE-derived tumors in L particle-injected rats was significantly suppressed, but not of the non-hepatic tumor control. In summary, this is the first demonstration that nanoparticles could be used for delivery of therapeutic genes with anti-tumor activity into human liver tumors. This intravenous delivery system may be one of the major advantages as compared to many other viral vector systems.

Animals↗
PubMed2006

Biphasic clinical course and early white matter abnormalities may be indicators of neurological sequelae after status epilepticus in children.

Clinical course and serial neuroimaging findings are not fully described in children who have had neurological sequelae following status epilepticus. We found four patients who had neurological sequelae out of 42 children with status epilepticus in 2004. MRI studies were reviewed with specific attention to diffusion-weighted images (DWI) and the apparent diffusion coefficient (ADC). Proinflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6, were measured in the cerebrospinal fluid (CSF) (3 patients). The clinical course showed biphasic; initial status epilepticus and neurological exacerbation along with seizure recurrence four to five days after onset. Within three days after initial status epilepticus, CT (all patients) and MRI (2 patients) did not show any abnormalities. From four to ten days after onset, MRI demonstrated diffuse hyperintensity in the cerebral white matter on DWI and hypointensity on ADC maps in all patients. Diffuse brain atrophy progressed thereafter. Tumor necrosis factor-alpha or interleukin-6 was elevated in all patients. A biphasic clinical course may be a specific feature for neurological sequelae. The preferential white matter involvement on MRI and elevated CSF cytokines indicate that glial dysfunction may play an important role in the pathophysiology of status epilepticus-associated cerebral damage.

Brain Mapping↗
PubMed2006

Dysphagia-gastroesophageal reflux complex: complications due to dysfunction of solitary tract nucleus-mediated vago-vagal reflex.

We report on the complication of gastroesophageal reflux (GER) in four patients with lower brainstem dysfunction. These patients suffered from perinatal asphyxia, cerebellar hemorrhage, or congenital dysphagia of unknown origin and showed facial nerve palsy, inspiratory stridor due to vocal cord paralysis, central sleep apnea, and dysphagia, in various combinations. Naso-intestinal tube feeding was introduced in all of the patients due to recurrent vomiting and aspiration pneumonia resulting from GER. T2-weighted magnetic resonance (MR) imaging revealed symmetrical high intensity lesions in the tegmentum of the lower pons and the medulla oblongata in two of the patients, and pontomedullary atrophy in another patient. In normal subjects, lower esophageal sphincter contraction is provoked by distension of the gastric wall, through a vago-vagal reflex. Since this reflex arc involves the solitary tract nucleus, where the swallowing center is located, the association of dysphagia and GER in the present patients is thought to result from the lesions in the tegmentum of medulla oblongata. We propose the term "dysphagia-GER complex" to describe the disturbed motility of the upper digestive tract due to lower brainstem involvement. In children with brainstem lesions, neurological assessment of GER is warranted, in addition to the examination of other signs of brainstem dysfunction, including dysphagia and respiratory disturbance.

Child, Preschool↗
PubMed2006

Effects of phthalate esters on the sensitization phase of contact hypersensitivity induced by fluorescein isothiocyanate.

BACKGROUND: Many different types of phthalate ester are used as plasticizers and are thus found in the air. There have been several studies that suggest an association between allergies and phthalate esters. We previously found that di-butyl phthalate (DBP) has an adjuvant effect in a mouse contact hypersensitivity model, in which fluorescein isothiocyanate (FITC) is involved as an immunogenic hapten. OBJECTIVE: We examined whether other phthalate esters enhance the process of sensitization to FITC by facilitating the trafficking of FITC-presenting dendritic cells or macrophages from skin sites to draining lymph nodes. METHODS: Mice were epicutaneously sensitized with FITC dissolved in acetone containing a phthalate ester. Sensitization was evaluated as ear swelling after a challenge with FITC. Draining lymph node cells obtained 24 h after skin sensitization were examined for FITC fluorescence by means of flow cytometry. FITC-positive cells were characterized with anti-CD11c and anti-CD11b by three-colour flow cytometry. RESULTS: When mice were sensitized with FITC in acetone containing DBP or di-n-propyl phthalate (DPP), strong enhancement of the ear-swelling response was observed. Di-methyl phthalate (DMP) and di-ethyl phthalate (DEP) were less effective but produced some enhancement. Consistent enhancement was not observed with di-(2-ethylhexyl) phthalate or di-isononyl phthalate. Upon sensitization in the presence of DBP or DPP, the number of FITC-positive dendritic cells (total CD11c+ as well as CD11c+/CD11b+) was increased in draining lymph nodes. As to the other four phthalate esters, there was no significant increase in the FITC-positive cell number in the draining lymph nodes. CONCLUSION: During the process of sensitization to FITC, DBP, and DPP exert strong adjuvant effects that are associated with enhancement of trafficking of antigen-presenting dendritic cells from the skin to draining lymph nodes.

Air Pollutants↗
PubMed2004

Enantioselective transesterification using immobilized Aspergillus oryzae overexpressing lipase.

In the present study, we used gene manipulation to construct a recombinant Aspergillus oryzae strain overexpressing lipase and investigated its application to the optical resolution of chiral compounds. A. oryzae niaD300, which was derived from the wild-type strain RIB40, was used as the host strain. The tglA gene, which encodes a triacylglycerol lipase, was cloned from the A. oryzae niaD300 chromosomal genome, then reintroduced, with and without a secretion-signal sequence, into the genome and expressed under the control of the improved glaA promoter of plasmid pNGA142. The resulting recombinant strain overexpressing A. oryzae lipase was immobilized within biomass-support particles and used as a whole-cell biocatalyst. The immobilized lipase-overexpressing strain with secretion-signal sequence showed high activity and was used to selectively synthesize (R)-1-phenylethyl acetate from (RS)-1-phenylethanol and vinyl acetate. After 48 h reaction at 30 degrees C with molecular sieve 4A, the yield and enantiomeric excess (%ee) of (R)-1-phenylethyl acetate reached approximately 90 and 95%ee, respectively. The whole-cell biocatalyst for optical resolution of chiral compounds produced in this study maintained its activity over 25 batch-reaction cycles.

Aspergillus oryzae↗
PubMed2004

Over-expression system for secretory phospholipase D by Streptomyces lividans.

The structural gene for phospholipase D (PLD) of an actinomycete, Streptoverticillium cinnamoneum, together with its promoter region was introduced into Streptomyces lividans using a shuttle vector-pUC702-for Escherichia coli and S. lividans. The transformant was found to secrete a large amount of PLD (about 2.0x10(4) U/l, 42 mg/l) when cultured in a jar fermentor. Both an initial glucose concentration of 17.5 g/l and the feeding of carbon and nitrogen sources are effective for efficient secretion of PLD; under these culture conditions, the amount of PLD secreted reached a maximum level (about 5.5x10(4) U/l, 118 mg/l) after about 60 h. In contrast to the original producer, Stv. cinnamoneum, which secretes only a small amount of PLD (about 1.1x10(3) U/l, 2 mg/l) along with other extracellular proteins, this heterologous expression system is markedly more efficient in production of secretory PLD.

Actinobacteria↗
PubMed2004

Yeast cell-surface display--applications of molecular display.

In a cell-surface engineering system established using the yeast Saccharomyces cerevisiae, novel, so-called arming yeasts are constructed that are armed with biocatalysts in the form of enzymes, functional proteins, antibodies, and combinatorial protein libraries. Among the many advantages of the system, in which proteins are genetically displayed on the cell surface, are easy reproduction of the displayed biocatalysts and easy separation of product from catalyst. As proteins and peptides of various kinds can be displayed on the yeast cell surface, the system is expected to allow the preparation of tailor-made functional proteins. With its ability to express many of the functional proteins necessary for post-translational modification and in a range of different sizes, the yeast-based molecular display system appears uniquely useful among the various display systems so far developed. Capable of conferring novel additional abilities upon living cells, cell-surface engineering heralds a new era of combinatorial bioengineering in the field of biotechnology. This mini-review describes molecular display using yeast and its various applications.

Agglutinins↗
PubMed2004

Analysis of prognostic factors after surgery for stage III and IV gallbladder cancer.

AIM: Survival and prognostic factors were analysed in patients who had undergone surgical resection with curative intention with the aim of identifying groups of patient with stage III and IV gallbladder cancer on the TNM classification who might benefit from surgery. METHODS: Thirty-seven patients with advanced gallbladder cancer were studied, the cumulative survival rate for each group was calculated for each pTNM factor. RESULTS: The 5-year survival rates in the stage III patients were 83.3%, while those for the stage IVA patients were 46.2%, and those for the stage IVB patients 16.7%. CONCLUSIONS: In patients with invasion of adjacent organs, including the liver and gastrointestinal tract, and rated as pT3 or pT4, extended surgery excising the invaded tissue may be justified. In patients with pN2 lymph-node metastasis, even without adjacent organ invasion, radical surgery may not achieve a good outcome.

Aged↗
PubMed2003

Enantioselective transesterification using lipase-displaying yeast whole-cell biocatalyst.

An enantioselective transesterification in non-aqueous organic solvent was developed by utilizing a lipase-displaying yeast whole cell biocatalyst constructed in our previous study. As a model reaction, optical resolution of (RS)-1-phenylethanol, which serves as one of chiral building blocks, was carried out by enantioselective transesterification with vinyl acetate. Recombinant Rhizopus oryzae lipase displayed on the yeast cell surface retained its activity in hexane, heptane, cyclohexane and octane. The effective amount of whole-cell biocatalyst in the reaction mixture was 10 mg/ml solvent. In a reaction mixture incubated for 36 h with molecular sieves 4A, the concentration of (R)-1-phenylethyl acetate reached 39.8 mM (97.3% yield) with high enantiomeric excess (93.3%ee). In contrast, a reaction mixture incubated without molecular sieves 4A produced little (R)- and (S)-1-phenylethyl acetate. The results obtained in this study demonstrate the applicability of the lipase-displaying yeast whole cell biocatalyst to bioconversion processes in non-aqueous organic solvents.

Benzyl Alcohols↗
PubMed2003

Affinity selection of target cells from cell surface displayed libraries: a novel procedure using thermo-responsive magnetic nanoparticles.

Biotinylated thermo-responsive magnetic nanoparticles for use in affinity selection from yeast cell surface display libraries were prepared by coating magnetite nanoparticles with a thermo-responsive polymer consisting of N-isopropyl acrylamide and a biotin derivative. These particles showed a reversible transition between flocculation and dispersion at around the lower critical solution temperature of 30 degrees C, above which the flocculated particles--which absorbed a large amount of avidin due to their large surface area--were quickly separable by magnet. The model library was constructed by mixing control yeast cells with target yeast cells co-displaying IgG binding protein (ZZ) and enhanced green fluorescence protein. Biotinylated IgG and avidin were subsequently added to the model library, and target cells were efficiently enriched with the biotinylated magnetic nanoparticles by avidin-biotin sandwich and ZZ-IgG interaction. The few target cells (0.001%) in the model library were enriched by up to 100% in only 5 days by an affinity selection procedure repeated four times. This novel method based on magnetic nanoparticles and a yeast cell surface display system could fulfill a wide range of applications in the analysis of protein-protein interactions and rapid isolation of novel biomolecules.

Avidin↗
PubMed2003

Display of a functional hetero-oligomeric catalytic antibody on the yeast cell surface.

A functional hetero-oligomeric protein was, for the first time, displayed on the yeast cell surface. A hetero-oligomeric Fab fragment of the catalytic antibody 6D9 can hydrolyze a non-bioactive chloramphenicol monoester derivative to produce chloramphenicol. The gene encoding the light chain of the Fab fragment of 6D9 was expressed with the tandemly-linked C-terminal half of alpha-agglutinin. At the same time, the gene encoding the Fd fragment of the heavy chain of the Fab fragment was expressed as a secretion protein. The combined Fab fragment displayed and associated on the yeast cell surface had an intermolecular disulfide linkage between the light and heavy chains. This protein fragment catalyzed the hydrolysis of a chloramphenicol monoester derivative and exhibited high stability in binding with a transition-state analog (TSA). The catalytic reaction was also inhibited by the TSA. The successful display of a functional hetero-oligomeric catalytic antibody provides a useful model for the display of hetero-oligomeric proteins and enzymes.

Antibodies, Catalytic↗
PubMed2003

Anti-annexin A5 antibodies in reproductive failures in relation to antiphospholipid antibodies and phosphatidylserine.

PROBLEM: The presence of IgG anti-annexin A5 (IgGalphaA5) and/or antiphospholipid antibodies (aPL) are risk factors associated with recurrent spontaneous abortion. Problems are whether IgA antiannexin A5 (IgAalphaA5) is pathogenic, and how IgGalphaA5 works. METHOD OF STUDY: Blood samples from 238 patients with early recurrent spontaneous abortion, 48 patients with recurrent in vitro fertilization-embryo transfer failure, 179 non-pregnant women and 120 pregnant controls were tested for IgAalphaA5 by enzyme-linked immunosorbent assay. We also determined if IgGalphaA5 appeared coincident with aPL. The antigenic epitope(s) recognized by IgGalphaA5 was investigated. RESULTS: We observed no difference between patients and controls for IgAalphaA5. The prevalence of IgGalphaA5 was not different statistically between patient samples with or without aPL. Patient IgGalphaA5 bound annexin A5 when the latter was free/unbound but not when annexin A5 was associated with phospholipid. CONCLUSIONS: The IgAalphaA5 does not appear to be pathogenic. IgGalphaA5 works to make a complex with annexin A5 without relation to aPLs, which may reduce annexin A5 available for binding to trophoblast.

Abortion, Spontaneous↗
PubMed2002

Long anchor using Flo1 protein enhances reactivity of cell surface-displayed glucoamylase to polymer substrates.

We investigated the influence of anchor length on the reactivity to polymer substrate of enzyme displayed on yeast cell surfaces. Using various lengths [42, 102, 146, 318, 428, and 1,326 amino acids (aa)] of the C-terminal region of the Saccharomyces cerevisiae Flo1 protein (Flo1p), which plays a major role in yeast flocculation, six display systems with various anchor lengths were constructed. In these systems, the target protein was displayed on the yeast cell surface under the control of the 5'-upstream region of the isocitrate lyase gene of Candida tropicalis ( UPR-ICL). Cell-surface display of Rhizopus oryzae glucoamylase by these systems was induced and confirmed in all systems by immunofluorescence microscopy and immunoblotting. Flow-cytometer measurement of the fluorescence intensity of immunofluorescence-labeled yeast cells displaying glucoamylase indicated that glucoamylase displayed with longer anchors, especially those of 428 and 1,326 aa in length, had higher reactivity to antibodies. The reactivity of starch to displayed glucoamylase, which was evaluated by plate assay, increased with anchor length, as did the cell growth-rate in starch-containing medium. These results indicate that cell-surface display systems using 428- and 1,326-aa length anchors of Flo1p are effective for the display of enzymes on the outer surface of yeast cells.

Cloning, Molecular↗
PubMed2002

High-level ethanol production from starch by a flocculent Saccharomyces cerevisiae strain displaying cell-surface glucoamylase.

A Strain of host yeast YF207, which is a tryptophan auxotroph and shows strong flocculation ability, was obtained from SaccharomYces diastaticus ATCC60712 and S. cerevisiae W303-1B by tetrad analysis. The plasmid pGA11, which is a multicopy plasmid for cell-surface expression of the Rhyzopus oryzae glucoamylase/alpha-agglutinin fusion protein, was then introduced into this flocculent yeast strain (YF207/pGA11). Yeast YF207/pGA11 grew rapidly under aerobic condition (dissolved oxygen 2.0 ppm), using soluble starch. The harvested cells were used for batch fermentation of soluble starch to ethanol under anaerobic condition and showed high ethanol production rates (0.71 g h(-1) l(-1)) without a time lag, because glucoamylase was immobilized on the yeast cell surface. During repeated utilization of cells for fermentation, YF207/pGA11 maintained high ethanol production rates over 300 h. Moreover, in fed-batch fermentation with YF207/pGA11 for approximately 120 h, the ethanol concentration reached up to 50 g l(-1). In conclusion, flocculent yeast cells displaying cell-surface glucoamylase are considered to be very effective for the direct fermentation of soluble starch to ethanol.

Aerobiosis↗
PubMed2002

The cellular pharmacology of oxaliplatin resistance.

Oxaliplatin is a third generation platinum compound that differs from cisplatin and carboplatin in having a broader spectrum of antitumour activity. Molecular studies suggest that oxaliplatin adducts are recognised and processed differently than those produced by the earlier generation Pt-containing drugs. We report here studies on the kinetics of the development of oxaliplatin resistance, and the changes in the cellular pharmacology of oxaliplatin that accompany the emergence of the resistant phenotype in five parental human tumour cell lines and their sub-lines selected for acquired oxaliplatin resistance in vitro. During selection, resistance did not substantially increase until after at least six cycles of oxaliplatin treatment. Oxaliplatin demonstrated schedule-dependency with a 1-h exposure being substantially less cytotoxic than a continuous exposure. Whole cell uptake was linear with concentration, but uptake in the resistant cells averaged only 27+/-10 S.D.% of that in the sensitive cells. Pt accumulation in DNA was markedly reduced in four of the five resistant cell lines, but this did not correlate with either IC(50) or total cellular accumulation. Four of the five resistant sub-lines also demonstrated increased tolerance to adducts in DNA that ranged from 3.1 to 7.6-fold. We conclude that development of acquired resistance to oxaliplatin is accompanied by independent defects in both whole cell uptake and in adduct formation.

Antineoplastic Agents↗