From bench to bedside: diagnosis of Gitelman's syndrome -- defect of sodium-chloride cotransporter in renal tissue.
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Adolescent↗
Biomedical subjects
Y K Oh
Publications and source records attributed to Y K Oh.
Improvement of the thickening and dewatering characteristics of activated sludge by electroflotation (EF).
The performances of electroflotation (EF) on the thickening of activated sludge were investigated using laboratory scale batch flotation reactors. Four activated sludges including bulking sludges were tested. After 30 minutes of EF operation, 57-84% of sludge volume reduction could be achieved by EF, while only about 1.5-14% could be obtained by gravity thickening for the same period. After thickening the effluent water quality in terms of TCOD, SS, and turbidity was improved by EF operation for all sludge samples. In addition, the EF thickened sludge showed much better dewaterability both in SRF and cake solid content. It is induced that the air bubbles entrapped in the thickened sludge play a key role in the observed dewaterbility improvement.
Electrochemistry↗
Denitrification and phosphorus release under anoxic conditions in an anoxic-anaerobic-aerobic BNR process.
An anoxic-anaerobic-aerobic biologial nutrient removal process was used in this study. The kinetic aspects of denitrification and phosphorus release under anoxic conditions were investigated by conducting a pilot-scale plant operation under various SRTs (solids retention times), HRTs (hydraulic retention times) and internal recycle ratios. The process was capable of completely denitrifying the NOx- -N (the sum of NO2- -N and NO3- -N) in the nitrified recycle, resulting in an NOx- -N concentration of less than 1.0 mg l(-1) N in the anoxic zones. Denitrification and phosphorus release were accomplished due to abundant organic substrates in the anoxic zone at the head end of the process and achieved approximately equivalent rates with respect to influent SCOD loading in the zone. Phosphorus release continued without any nitrate inhibition due to low NOx- -N concentrations of less than 2.0 mg l(-1) N in the anaerobic zone.
Bacteria, Aerobic↗
Nasal absorption and biodistribution of plasmid DNA: an alternative route of DNA vaccine delivery.
Nasal administration is emerging as a new route of DNA vaccine delivery. We aimed to study the extent of absorption and biodistribution of intranasally administered plasmid DNA. After intranasal administration, the level of plasmid DNA in the serum peaked at 1.5 h. The ratio of the area under the concentration (AUC) after intranasal administration of DNA over the AUC after intravenous administration was 0.14. At 15 min post inoculation, the highest organ distribution was observed in the liver and the cervical lymph nodes showed the highest level among the lymph nodes. At 24 h a higher localization of plasmids to the brain than to the lung and spleen was notable. A significant level of mRNA expression was observed in the lymph nodes. These results suggest that plasmid DNA can be substantially absorbed and distributed to the lymph nodes after intranasal administration, partly explaining the systemic immunogenicity of intranasally administered plasmid DNA vaccines.
Administration, Intranasal↗
Effects of vehicles and enhancers on transdermal delivery of melatonin.
For a more effective transdermal delivery of melatonin (MT), the effects of vehicles and enhancers on its skin permeation and lag time were evaluated. Skin permeation study was conducted in Franz diffusion cells using excised hairless mouse skins. MT was analyzed by HPLC. As vehicles, ethanol (EtOH), polyethylene glycol 400 (PEG), or propylene glycol (PG) was used alone or mixed with a phosphate buffer. Binary vehicles (EtOH/buffer, PEG/buffer, PG/buffer) showed different effects on the skin permeation of MT and its lag time. Compared with the buffer alone, the PEG/buffer shortened the lag time of MT but reduced its skin permeation. EtOH/buffer significantly increased the flux of MT but prolonged the lag time with the content of EtOH. PG/buffer did not affect the lag time but slightly increased the skin permeation of MT at the higher content of PG (> or =80%). These results indicate that the composition of vehicles exerts significant influence but it per se might have limitation in modulating the transdermal delivery of MT. Next, one tested whether fatty acids could more effectively enhance the skin permeation of MT and shorten its lag time. Given the influence of vehicles on both permeation and lag time, PG was used as a vehicle for fatty acids. The permeation-enhancing effects of saturated fatty acids increased in the following order: C10>C12>C14>C16>C18. The saturated fatty acid, however, did not significantly shorten the lag time regardless of the carbon chain length. Meanwhile, similar to saturated lauric acid (C12), unsaturated oleic acid (C18) dramatically enhanced the skin permeability coefficient of MT more than 950-fold over the effect of PG alone. Moreover, oleic acid showed the shortest lag time (2.1 h). The results suggest that oleic acid in a suitable vehicle could more effectively enhance the skin permeation of MT and shorten its lag time than did the vehicles of various compositions.
Animals↗
Nuclear factor-kappa B plays a major role in the regulation of chemokine expression of HeLa cells in response to Toxoplasma gondii infection.
Toxoplasma gondii infection results in an infiltration of immune cells. The mechanisms responsible for triggering inflammatory cell infiltration in T. gondii infection are not fully understood. We report that T. gondii-infected HeLa cells induced nuclear factor-kappa B (NF-kappaB) activation and increased the expression of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) mRNA. An inhibitor of NF-kappaB activation, calpain-1 inhibitor, blocked the chemokine secretion induced by live T. gondii. Activation of the IL-8 and NF-kappaB transcriptional reporters was suppressed in cells co-transfected with IkappaB kinase beta and the IkappaBalpha super-repressor plasmids. Moreover, the addition of IL-1alpha increased NF-kappaB activation and IL-8 mRNA expression in T. gondii-infected HeLa cells. These results suggest that NF-kappaB is a central regulator of the chemokine response in T. gondii-infected human epithelial cells and that chemokine IL-8 and MCP-1 secretion might be involved in the pathogenesis of T. gondii, via the recruitment of neutrophils, monocytes, and lymphocytes.
Animals↗
Once-a-day oral dosing regimen of cyclosporin A: combined therapy of cyclosporin A premicroemulsion concentrates and enteric coated solid-state premicroemulsion concentrates.
PURPOSE: To develop once-a-day oral dosing regimen that provides the blood levels of cyclosporin A (CsA) in the therapeutic ranges over 24 hours. METHODS: CsA premicroemulsion concentrates (preME) were formulated from phase diagrams. Enteric-coated solid-state premicroemulsion concentrates (sME) were prepared by coating preME with enteric-coating matrials and solidifying them. CsA was measured using high-performance liquid chromatography or radioimmunoassay. RESULTS: PreME consisted of CsA, oil, and mixture of surfactants and a cosurfactant. PreME spontaneously formed microemulsions in aqueous medium and showed oral absorption profiles similar to Sandimmune Neoral in dogs. Dispersion of sME in aqueous medium also formed microemulsions. Release rates of CsA from sME depended on pH and the type of enteric-coating materials and highly correlated with the extent of oral absorption. The co-administration of preME and sME (200 mg CsA) showed the maximum blood level of CsA not significantly different from that of preME (100 mg CsA) and the concentration of CsA close to the minimum therapeutic level at 24 hours. CONCLUSIONS: The combined treatment of preME and sME provided controlled oral absorption of CsA over a 24-hour period. Such once-a-day dosing regimens will lead to increased patient compliance and reduced episodes of organ rejection after transplantation.
Administration, Oral↗
Prolonged organ retention and safety of plasmid DNA administered in polyethylenimine complexes.
Polyethylenimine (PEI) has been studied as an efficient nonviral gene transfer vector. Here, we report the biodistribution fates and safety of plasmid DNA intravenously administered in PEI complexes. Using pCMVbeta as a model gene, the biodistribution of plasmid DNA was measured by quantitative polymerase chain reaction. A deletion mutant of pCMVbeta was used as an internal standard. After intravenous administration of PEI/DNA complexes, the serum levels of DNA rapidly declined for up to 15 min. However, after this point, the serum levels of DNA diminished slowly. At 15 min after dose, PEI/DNA complexes showed 33-fold higher distribution of DNA in the lung than did naked DNA. At 24 h, all the organs tested showed much higher levels of plasmid DNA in PEI/DNA complexes, with distribution in the liver and lung being three orders of magnitude higher than naked DNA. The mRNA expression of DNA was observed in various organs of PEI/DNA-treated mice at 12 days after dose. Once a week dosing of PEI/DNA complexes over 3 consecutive weeks did not alter the histology of the organs. However, twice a week dosing over 3 weeks induced a sign of inflammation in the liver. These results indicate that PEI enhances the delivery and retention of plasmid DNA in the organs, especially the liver, but that safe delivery requires proper dosing intervals.
Animals↗
Polarized secretion of CXC chemokines by human intestinal epithelial cells in response to Bacteroides fragilis enterotoxin: NF-kappa B plays a major role in the regulation of IL-8 expression.
Enterotoxigenic B. fragilis, which produces a approximately 20 kD heat-labile toxin (BFT), has been associated with diarrhoeal diseases and mucosal inflammation. To determine if epithelial cells can contribute to BFT-induced inflammation, we assessed the expression of CXC chemokines by BFT-stimulated human intestinal epithelial cells. BFT stimulation increased expression of the neutrophil chemoattractant and activators ENA-78, GRO-alpha, and IL-8. Up-regulated chemokine mRNA expression was paralleled by increased protein levels. Activation of the IL-8 and NF-kappa B transcriptional reporters was inhibited in cells cotransfected with the I kappa B kinase beta and IkB alpha superrepressor plasmids. Whereas lactate dehydrogenase, which was used to monitor cell lysis, was released predominantly from the apical surface, CXC chemokines were predominantly secreted from the basolateral surface of BFT-treated epithelial cells. The basolateral secretion of CXC chemokines from BFT-stimulated colon epithelial cells suggests that these chemokines can contribute to the inflammatory cell infiltrate in the underlying intestinal mucosa.
Bacterial Toxins↗
Effects of presurgical and post-surgical irradiation on the healing process of Medpor in dogs.
The purpose of this study was to determine the effect of irradiation on the healing process and the effect on the contact surface of Medpor and bone. Eighteen dogs were studied. The animals were divided into three groups. Six non-irradiated dogs served as controls (Group 1). Twelve dogs irradiated on the left femur, before and after implantation of Medpor, were studied. The dogs were euthanized 4 and 8 weeks after Medpor was implanted in presurgical irradiation subgroup animals (Group 2) and after the completion of irradiation in post-surgical irradiation subgroup animals (Group 3). Light microscopic and scanning electron microscopic examinations were performed. The appearance of osteoblasts and bone matrix formation were remarkably late and manifest slight reactions in post-surgical irradiation group compared to the control group presenting the osteoblasts at 4 weeks, and those osteoblasts were not visible in presurgical irradiation group in both the 4-week and 8-week observation. We concluded that the bone remodeling was delayed in the irradiated bone, especially in the presurgical group.
Animals↗
Atypical bone metastasis and radiation changes in a colon cancer: a case report and a review of the literature.
We report a unique case of skeletal metastasis with prominent soft tissue extension from a colon cancer in a 44-year-old male patient. Four years after the diagnosis of colon cancer, plain radiographic examinations revealed a prominent soft tissue mass associated with cortical destruction of the right femur. Palliative radiotherapy of the right femur was performed. After completing radiotherapy, massive remineralization was seen in the soft tissue component. With the assistance of pre- and post-radiotherapy computerized tomography images, obtained in the process of planning the radiotherapy, we reached the conclusion that in our case the pre-radiotherapy finding was an extreme case of eccentric expansion of the bony cortex due to the outgrowth of bony metastasis. Retrospectively, the initial prominent soft tissue mass associated with the cortical destruction seems to have been a protruding bone metastasis, extending from the medial aspect of the right femur. This peculiar feature with remineralization after radiotherapy should help explain the phenomenon of atypical bony metastasis from a radiological perspective.
Adenocarcinoma↗
Agreement rates among single photon emission computed tomography using gallium-67, computed axial tomography and lymphangiography for Hodgkin disease and correlation of image findings with clinical outcome.
BACKGROUND: This study was undertaken to systematically evaluate the agreement rates among single photon emission computed tomography using gallium-67 (Ga-67 SPECT), lymphangiography (LAG), and computed axial tomography (CT) scan findings for Hodgkin disease and to correlate radiologic findings with clinical outcome. METHODS: One hundred three previously untreated patients with Hodgkin disease who had Ga-67 SPECT scan between August 1992 and December 1994 at our institution form the basis of this study. The agreement rates among Ga-67 SPECT, LAG, and CT scan findings were calculated by sites from the pretreatment evaluation throughout the courses of chemotherapy. The probabilities of recurrence or progression by sites were correlated with the radiologic findings. RESULTS: The median follow-up was 3 years. The pretreatment agreement ranged from 75% to 100% between Ga-67 SPECT and CT scans, 85-100% between CT scan and LAG, and 74-99% between Ga-67 SPECT and LAG. A greater variation in agreement was observed once chemotherapy was started, the site with the least agreement being the mediastinum. The most common site of the recurrence or progression was also the mediastinum. When the CT scan showed persistent abnormality even after Ga-67 SPECT turned negative after chemotherapy, the chances of mediastinal recurrence or progression were 3 in 34 and 3 in 18 after 1-3 cycles and 4-6 cycles, respectively. CONCLUSIONS: Although there was a relatively high correlation between Ga-67 SPECT and the other modalities, the intrinsic limitation of planar Ga-67 was still observed in Ga-67 SPECT especially in the mediastinum. There was still a moderate risk of mediastinal recurrence or progression even after residual CT scan abnormality lost gallium avidity from chemotherapy.
Adolescent↗
Effect of pentoxifylline on radiation response of non-small cell lung cancer: a phase III randomized multicenter trial.
PURPOSES: The objectives of this prospective clinical trial were to determine whether pentoxifylline improves the radiation response and survival in patients with non-small cell lung cancer. MATERIALS AND METHODS: From July 1993 through October 1994, 64 patients with histologically confirmed Stage I, II and III non-small cell lung cancer were randomly divided into pentoxifylline (Pento)+Radiotherapy (RT) group and RT alone group. Out of the 64 patients, only 47 patients who had measurable tumors on chest X-ray views were analyzed and divided into Pento+RT group (n=27) and RT alone group (n=20). Total tumor dose of 65-70 Gy was delivered as conventional fractionated radiation schedules. Pento was given to the patients 3 x 400 mg/day with a daily dose of 1200 mg during RT. RESULTS: Complete response (CR), partial response (PR), and stable in Pento+RT group were three (11%), 13 (48%), and 11 (41%), respectively, as compared with corresponding values of three (15%), 13 (65%), and four (20%) in the RT alone group. The median time to relapse in the Pento+RT group was 11 months which was 2 months longer than for the RT alone group (P>0.05). All the patients in both groups showed lower than or equal to grade 2 dysphagia, odynophagia, pulmonary fibrosis, and pneumonitis. The median survival was 18 months in the Pento+RT group and 7 months in the RT alone group. The 1-year survival rate was 60% in the Pento+RT group and 35% in the RT alone group, the 2-year survival rate was 18% in the Pento+RT group and 12% in the RT alone group. But these differences were not statistically significant (P>0.05). CONCLUSION: We concluded that Pento is a modestly effective radiation response modifier and provide benefit in the treatment of non-small cell lung cancer.
Aged↗
Seasonal biochemical plasticity of a flight muscle in a bat, Murina leucogaster.
Cellular and biochemical responses of the pectoral muscle to variation in seasonal activity were studied in the bat, Murina leucogaster ognevi. We collected bats in mid-hibernation (February), end-hibernation (April), and mid-summer (August) to track major activity periods in their annual cycle. Our findings indicated that myofiber cross-sectional area decreased to 68% between mid- and end-hibernation, but returned to the winter level in mid-summer. Total soluble protein and total RNA concentrations were not altered over these sampling periods. Oxidative potential gauged by citrate synthase activity increased 1.47-fold from mid- to end-hibernation and then remained at the similar level in mid-summer. Glycolytic potential gauged by lactate dehydrogenase activity changed little between mid- and end-hibernation but increased 1.42-fold in summer, compared with the winter level. Thus, the myofibers underwent disuse atrophy during hibernation, while enzymatic catalytic function recovered towards the level of mid-summer.
Adenosine Triphosphatases↗
Synergistic depletion of astrocytic glutathione by glucose deprivation and peroxynitrite: correlation with mitochondrial dysfunction and subsequent cell death.
Previously we reported that immunostimulated astrocytes were highly vulnerable to glucose deprivation. The augmented death was mimicked by the peroxynitrite (ONOO )-producing reagent 3-morpholinosydnonimine (SIN-1). Here we show that glucose deprivation and ONOO- synergistically deplete intracellular reduced glutathione (GSH) and augment the death of astrocytes via formation of cyclosporin A-sensitive mitochondrial permeability transition (MPT) pore. Astrocytic GSH levels were only slightly decreased by glucose deprivation or SIN-1 (200 microM) alone. In contrast, a rapid and large depletion of GSH was observed in glucose-deprived/ SIN-1-treated astrocytes. The depletion of GSH occurred before a significant release of lactate dehydrogenase (a marker of cell death). Superoxide dismutase and ONOO-scavengers completely blocked the augmented death, indicating that the reaction of nitric oxide with superoxide to form ONOO was implicated. Furthermore, nitrotyrosine immunoreactivity (a marker of ONOO-) was markedly enhanced in glucose-deprived/SIN-1 -treated astrocytes. Mitochondrial transmembrane potential (MTP) was synergistically decreased in glucose-deprived/SIN-1-treated astrocytes. The glutathione synthase inhibitor L-buthionine-(S,R)-sulfoximine markedly decreased the MTP and increased lactate dehydrogenase (LDH) releases in SIN-1-treated astrocytes. Cyclosporin A, an MPT pore blocker, completely prevented the MTP depolarization as well as the enhanced LDH releases in glucose-deprived/SIN-1-treated astrocytes.
Animals↗
Overexpression, crystallization and preliminary X-ray crystallographic analysis of dihydrofolate reductase from bacteriophage T4.
Dihydrofolate reductase (DHFR) from bacteriophage T4 is a homodimer consisting of 193-residue subunits. It has been crystallized in the presence of the cofactor (NADPH) and an inhibitor (aminopterin) at 296 K using sodium chloride as precipitant. The crystals are tetragonal, belonging to the space group P4(1)22 (or P4(3)22), with unit-cell parameters a = b = 61.14, c = 123.23 A under cryogenic conditions. The asymmetric unit contains a single subunit, with a corresponding V(m) of 2.65 A(3) Da(-1) and a solvent content of 53. 6%. Native data have been collected from a crystal to 1.9 A resolution using synchrotron X-rays.
Bacteriophage T4↗
Expression of protein kinase C genes in normal (+/+) and W mutant alleles (Wsh/Wsh, W/Wv) mice testes.
In the present study, we investigated the expression of mRNA of protein kinase C (PKC) isoenzymes (alpha, beta, gamma, delta, epsilon, zeta, eta, and theta) in normal (+/+) and W mutant alleles mice testes. In +/+ mice testes, abundant expression of PKCdelta and PKCtheta was observed, while other PKCs (alpha, beta, gamma, epsilon, zeta, and eta) generally were not detected by Northern blotting. The PKCdelta and PKCtheta isoenzymes demonstrated a distinctive cellular distribution when evaluated by in situ hybridization. We have previously shown that PKCdelta gene was selectively expressed in spermatid of +/+ testes. Here we show that PKCdelta gene is also present in spermatid of Wsh/Wsh mice testes and PKCtheta gene was present in interstitial cells of +/+, Wsh/Wsh, and W/Wv mice testes. These studies provide the evidence of selective cell distributions of the PKC isoenzymes and suggest that PKC has the functional significance in testes.
Alleles↗
Adult T cell leukemia/lymphoma with lymphopenia in a Korean.
We experienced a case of adult T cell leukemia/lymphoma (ATLL) in a 48-year-old Korean female, who has never been abroad since birth and no history of blood transfusion. The patient had hypercalcemia and multiple lymphadenopathy. Histopathologic study of left cervical lymph node (LN) and bone marrow (BM) revealed that infiltrates of malignant lymphoid cells were composed of small, medium and large cells with pleomorphic nuclei. Smears of peripheral blood (PB) showed lymphopenia (16%) with the appearance of a few atypical lymphoid cells (less than 2%), but not the typical clover leaf cells seen in ATLL. Immunophenotypic study of LN and BM revealed T cell phenotype. PB showed increased CD4+ T cell (T(H), CD3/CD4+, 57%) and decreased CD8+ T cell counts (T(S), CD3/CD8+, 6.7%). The sera of the patient and her family were reactive for HTLV-I antibody. The specific sequences of pol, env, and tax of HTLV-I DNA were detected in the lymphoma cells and peripheral blood mononuclear cells (PBMC) using polymerase chain reaction. Ultrastructural examination of PBMC confirmed numerous type c virus particles in extracellular space. This case was an acute type of ATLL without overt leukemic features in PB. Despite chemotherapy and intensive conservative treatment, she died 3 months after admission.
Biopsy↗