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Biomedical subjects

M G Lee

Publications and source records attributed to M G Lee.

At least 109 records · Page 6Linked to original sources

Crystallization and preliminary X-ray analysis of Saccharomyces cerevisiae Ypd1p, a key intermediate in phosphorelay signal transduction.

Ypd1p, a 167-residue protein from Saccharomyces cerevisiae, plays a key role in osmosensing phosphorelay signal transduction. It forms part of a multistep phosphorelay system which also includes Sln1p hybrid histidine kinase and two response regulators, Ssk1p and Skn7p. It has been overexpressed in soluble form in Escherichia coli with a His6-tag at its C-terminus. The recombinant protein has been crystallized at room temperature using ammonium sulfate and lithium sulfate as precipitants. Native diffraction data have been collected to 2.3 A using synchrotron radiation. The crystals are triclinic, belonging to the space group P1, with unit-cell parameters a = 65.78, b = 66.74, c = 65.75 A, alpha = 106.60, beta = 106.48, gamma = 115. 53 degrees. The asymmetric unit contains four molecules of the monomeric recombinant Ypd1p, with a corresponding Vm of 2.75 A3 Da-1 and a solvent content of 55.3%.

Crystallization↗

Effect of probenecid on the renal excretion mechanism of a new carbapenem, DA-1131, in rats and rabbits.

The effects of probenecid, an anion transport inhibitor, on the renal excretion mechanism of a new anionic carbapenem, DA-1131, were investigated after a 1-min intravenous infusion of DA-1131 at 100 mg/kg of body weight to rabbits and 50 mg/kg to rats with or without probenecid at 50 mg/kg for both species. In control rabbits, the renal clearance (CLR) of DA-1131 and the glomerular filtration rate based on creatinine clearance (CLCR) were 6.14 +/- 2.09 and 2.26 +/- 0.589 ml/min/kg, respectively. When considering the less than 10% plasma protein binding of DA-1131 in rabbits, renal tubular secretion of DA-1131 was observed in rabbits. The CLR of DA-1131 (3. 87 +/- 0.543 ml/min/kg) decreased significantly with treatment with probenecid in rabbits, indicating that the renal tubular secretion of DA-1131 was inhibited by probenecid. However, in control rats, the CLR of DA-1131 (5.80 +/- 1.94 ml/min/kg) was comparable to the CLCR (4.29 +/- 1.64 ml/min/kg), indicating that DA-1131 was mainly excreted by glomerular filtration in rats. Therefore, it could be expected that the CLR of DA-1131 could not be affected by treatment with probenecid in rats; this was proved by a similar CLR of DA-1131 with treatment with (6.93 +/- 0.675 ml/min/kg) or without (5.80 +/- 1.94 ml/min/kg) probenecid. Therefore, the renal secretion of DA-1131 is a factor in rabbits but is not a factor in rats.

Animals↗

Effects of cilastatin on the pharmacokinetics of a new carbapenem, DA-1131, in rats, rabbits, and dogs.

DA-1131, a new carbapenem antibiotic, undergoes renal metabolism by renal dehydropeptidase I (DHP-I), located on the brush border of the proximal tubular cell. Species differences with regard to the effects of cilastatin, a renal DHP-I inhibitor, were investigated after a 1-min intravenous infusion of DA-1131, with or without cilastatin, to rats, rabbits, and dogs. After intravenous infusion, the nonrenal clearance (CL(NR)) of DA-1131 was significantly slower in rats (3.00 versus 8.01 ml/min/kg) and rabbits (2.41 versus 6.77 ml/min/kg) when the drug was coadministered with cilastatin; this could be due to the slower metabolism of DA-1131 by rat and rabbit kidney DHP-I. This indicated that renal metabolism of DA-1131 by renal DHP-I was inhibited by cilastatin. However, coadministration with cilastatin to dogs did not affect the CL(NR) of DA-1131.

Animals↗

Modified small-bowel follow-through: use of methylcellulose to improve bowel transradiance and prepare barium suspension.

PURPOSE: To evaluate the efficacy of barium suspension prepared in methylcellulose (MC) in modified small-bowel follow-through (SBFT). MATERIALS AND METHODS: The authors evaluated 155 patients who underwent modified SBFT with oral administration of MC after ingesting barium suspension. Of these patients, 52 received 40% suspension in MC, 46 received 40% suspension in water, and 57 received 70% suspension in water. Patients were divided into normal (n = 74) and abnormal (n = 81) groups according to the final results. The image quality, transit time to the cecum, and time to and frequency of flocculation were compared for both groups. RESULTS: In the normal group, the quality of the images in patients receiving 40% suspension in MC or 70% suspension in water was superior to that of images in patients receiving 40% suspension in water. In the abnormal group, the best image quality was achieved for the patients who received 40% suspension in MC. In the normal group, the difference in transit time between the three preparations was not substantial. In the abnormal group, however, the 40% suspension in MC showed the fastest transit time. Use of the 40% suspension in MC helped lower the frequency of flocculation in the normal group. CONCLUSION: Use of 40% barium suspension in MC is effective for improving the image quality in modified SBFT.

Barium Sulfate↗

Inflammatory pseudotumor of the liver in patients with recurrent pyogenic cholangitis: CT-histopathologic correlation.

PURPOSE: To correlate computed tomographic (CT) features of inflammatory pseudotumors of the liver with histopathologic results in patients with recurrent pyogenic cholangitis. MATERIALS AND METHODS: CT features of 13 cases of inflammatory hepatic pseudotumor in 10 patients with recurrent pyogenic cholangitis were reviewed. Diagnosis was made by means of surgical resection in all patients. CT scans were analyzed for the appearance of masses and ancillary findings in correlation with the histopathologic findings in each resected specimen. RESULTS: The masses were 2.0-7.0 cm (mean, 3.5 cm). At nonenhanced CT, the masses appeared as ill-defined, hypoattenuating lesions. At contrast material-enhanced CT, the masses exhibited central hypoattenuating areas with an iso- or hyperattenuating thickened periphery in four cases and a multiseptate appearance with hyperattenuating internal septa and periphery in nine cases. CT-histopathologic correlation showed that the central hypoattenuating area indicated the presence of chronic inflammatory infiltrates with foamy histiocytes, plasmacytes, and lymphocytes, while iso- or hyperattenuating areas in the periphery and internal septa of the mass represented fibroblastic proliferation. All patients had CT features of recurrent pyogenic cholangitis, such as hepatolithiasis, intrahepatic duct stricture and dilatation, common bile duct calculi, pneumobilia, or parenchymal atrophy. CONCLUSION: Although CT features are not specific, inflammatory pseudotumor should be included in the differential diagnosis in patients with recurrent pyogenic cholangitis and a hepatic mass detected at CT.

Adult↗

Multiple functional P2X and P2Y receptors in the luminal and basolateral membranes of pancreatic duct cells.

Purinergic receptors in the basolateral and luminal membranes of the pancreatic duct can act by a feedback mechanism to coordinate transport activity in the two membranes during ductal secretion. The goal of the present work was to identify and localize the functional P2 receptors (P2R) in the rat pancreatic duct. The lack of selective agonists and/or antagonists for any of the cloned P2R dictated the use of molecular and functional approaches to the characterization of ductal P2R. For the molecular studies, RNA was prepared from microdissected pancreatic intralobular ducts and was shown to be free of mRNA for amylase and endothelial nitric oxide synthase (markers for acinar and endothelial cells, respectively). A new procedure is described to obtain an enriched preparation of single duct cells suitable for electrophysiological studies. Localization of P2R was achieved by testing the effect of various P2R agonists on intracellular Ca(2+) concentration ([Ca(2+)](i)) of microperfused intralobular ducts. RT-PCR analysis suggested the expression of six subtypes of P2R in the pancreatic duct: three P2YR and three P2XR. Activation of Cl(-) current by various nucleotides and coupling of the receptors activated by these nucleotides to G proteins confirmed the expression of multiple P2R in duct cells. Measurement of [Ca(2+)](i) in microperfused intralobular ducts suggested the expression of P2X(1)R, P2X(4)R, probably P2X(7)R, and as yet unidentified P2YR, possibly P2Y(1)R, in the basolateral membrane. Expression of P2Y(2)R, P2Y(4)R, and P2X(7)R was found in the luminal membrane. The unprecedented expression of such a variety of P2R in one cell type, many capable of activating Cl(-) channels, suggests that these receptors may have an important role in pancreatic duct cell function.

Animals↗

Pharmacokinetics of a new proton-pump inhibitor, YJA-20379-8, after intravenous and oral administration to rats with streptozotocin-induced diabetes mellitus.

Because physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, were investigated after intravenous and oral administration of the drug (50 mg kg(-1)) to control rats and to rats with streptozotocin-induced diabetes mellitus (SIDM). After intravenous administration of YJA-20379-8 to SIDM rats, plasma concentrations of the drug were significantly higher and this resulted in a significantly greater AUC (area under the concentration-time curve; 2520 +/- 366 compared with 1870+/-272 microg min mL(-1)). This was because of significantly slower clearance (CL; 19.5+/-2.88 compared with 27.2+/-3.93 mL min(-1) kg(-1)) in SIDM rats. The significantly slower metabolism of YJA-20379-8 in SIDM rats was confirmed by an in-vitro tissue metabolism study; the amounts of YJA-20379-8 remaining in the liver (27.1+/-5.19 compared with 18.9+/-8.24 microg(g tissue)(-1)) were significantly greater after 30-min incubation of the drug (50 microg) with supernatant fractions obtained from the tissues by centrifugation at 9000 g. After oral administration of YJA-20379-8 to SIDM rats the plasma concentrations of the drug were significantly lower and this resulted in significantly smaller AUC (128+/-31.0 compared with 219+/-45.6 microg min mL(-1)). This was because of reduced gastrointestinal absorption of YJA-20379-8 in SIDM rats; the amounts of the oral dose recovered as unchanged drug from the entire gastrointestinal tract after 24h were significantly greater (32.9 compared with 19.2%) in SIDM rats. The tissue distribution of YJA-20379-8 was not affected by SIDM.

Administration, Oral↗

Gastrointestinal absorption of a new reversible proton pump inhibitor, YJA-20379-8, and its pharmacokinetics after oral administration in acetic acid-induced gastric ulcer in rats.

The absorption of YJA-20379-8 (3-butyryl-4-[5-(R)-(+)-methylbenzylamino]-8-ethoxy-1,7-naphthyrid ine) from various rat gastrointestinal segments was evaluated using in-situ closed-loops. The pharmacokinetics of the drug were also evaluated after oral administration to rats with acetic acid-induced gastric ulcer (AIURs). The concentrations of YJA-20379-8 in the biological samples were analyzed by HPLC. The absorption of YJA-20379-8 from stomach and jejunum was fast, but approximately 50% of the drug was recovered from each segment at 24 h. The total areas under the plasma concentration-time curves from time zero to 24h (AUC(0-24h)) were 161, 392, 233, 365, and 226 microg min mL(-1) for stomach, duodenum, jejunum, ileum, and colon, respectively. After oral administration of the drug, the plasma concentrations and the resultant AUC (0- 12h) were not significantly different between control and AIURs. The detection limits of YJA-20379-8 in human plasma and urine were 50 and 100 ng mL(-1), respectively. The results suggest that modification of the oral dose of YJA-20379-8 may not be required in gastric ulcer patients if the present rat pharmacokinetic data could be extrapolated to man.

Acetic Acid↗

Gastrointestinal first-pass effect of YJA-20379-8, a new reversible proton pump inhibitor, in rats.

Since low bioavailability of YJA-20379-8 (3-butyryl-4-[5-R-(+)-methylbenzylamino]-8ethoxy-1,7-naph thy ridine), a new reversible proton pump inhibitor, has been reported after oral administration of the drug to rats, the first-pass organ of the drug was investigated in rats. YJA-20379-8, 50 mg kg(-1), was infused over 1 min via the jugular vein (n=5) or the portal vein (n=5), or was instilled directly into the stomach (n=5) or the duodenum (n=5). After intravenous or intraportal infusion of the drug, the total body clearance of YJA-20379-8 (18.1 and 19.7 mL min(-1) kg(- 1) based on plasma data) was considerably lower than the reported cardiac output (296 mL min(-1) kg(-1) based on blood data) in rats. This data indicated that the first-pass effect of YJA-20379-8 by the lung and heart was negligible. The areas under the plasma concentration-time curve from time zero to time infinity (AUC) after intravenous or intraportal administration of YJA-20379-8 (2760 and 2540 microg min mL(-1)) were not significantly different, indicating that the hepatic first-pass effect of the drug was also negligible in rats. After intragastric or intraduodenal instillation of YJA-20379-8, the extent of absolute oral bioavailability was 18.2 and 33.8%, respectively. Based on gastrointestinal recovery studies, approximately 86.5 and 91.2% of YJA-20379-8 was absorbed from rat gastrointestinal tract after intragastric or intraduodenal instillation, respectively. The data indicated that gastrointestinal and intestinal first-pass effects of YJA-20379-8 were approximately 68% (86.5-18.2) and 57% (91.2-33.8), respectively. The AUC(0-24h) values of YJA-20379-8 were significantly different between intragastric and intraduodenal instillation, indicating that the gastric first-pass effect of the drug was approximately 10% in rats. Therefore, it could be concluded that the low F value of YJA-20379-8 after oral administration of the drug could be due to a considerable (approx. 60%) intestinal first-pass effect in rats.

Animals↗

Xanthogranulomatous cholecystitis: radiologic findings with histologic correlation that focuses on intramural nodules.

OBJECTIVE: The purpose of this study was to histologically classify intramural nodules associated with xanthogranulomatous cholecystitis and to evaluate the radiologic findings for each type of nodule. MATERIALS AND METHODS: Pathologic slides and radiologic studies including 14 sonographic and 16 CT examinations in 19 patients (12 men, seven women; mean age, 61 years) with xanthogranulomatous cholecystitis were reviewed. Radiologic findings were correlated with the histologic type of intramural nodule: abscess, xanthogranuloma, or a combination of the two. The duration of symptoms for each type of intramural nodule was also evaluated. RESULTS: Histologically, all patients had intramural nodules that were either abscesses (n = 11), xanthogranulomas (n = 5), or a combination of the two (n = 3). Radiologic studies revealed nodules in 10 patients (52.6%; four abscesses, four xanthogranulomas, and two combinations). For abscesses, the mean interval from onset of symptoms to surgery was 25 days; for xanthogranulomas, 70 days (p = .0057). Abscesses were associated with more complications of xanthogranulomatous cholecystitis. CONCLUSION: Intramural nodules in patients with xanthogranulomatous cholecystitis were found to represent abscesses or xanthogranulomas at histology. Xanthogranulomas were more often revealed radiologically than were abscesses. Abscesses caused more clinical complications. Because symptoms lasted longer for xanthogranulomas, we hypothesized that abscesses may become xanthogranulomas.

Adult↗

CT features of intraperitoneal manifestations of parasitic infestation.

OBJECTIVE: The purpose of this study was to evaluate the CT features of intraperitoneal manifestations with parasitic infestation in nine patients. CONCLUSION: The CT features of intraperitoneal manifestations of parasitic infestation were single or multiple multiseptated cystic masses in the peritoneal cavity, hazy omental infiltration, or both. Recognizing these features is important to establish an early diagnosis that leads to rapid treatment and helps avoid unnecessary surgery.

Female↗

Serologically diagnosed Lyme disease manifesting erythema migrans in Korea.

Lyme disease is a vector-borne infection, primarily transmitted by Ixodes ticks, and caused by Borrelia burgdorferi. It has a wide distribution in the northern hemisphere. In Korea, however, only one human case has been reported, although B. burgdorferi was isolated from the vector tick I. persulcatus in the region. A 60-year-old male and a 45-year-old female developed the clinical sign of erythema migrans. Each patients were bitten by a tick four weeks and five weeks, respectively, before entering the hospital. On serologic examination, significantly increased IgM and IgG antibody titers to B. burgdorferi were observed in consecutive tests performed at an interval of two weeks. They responded well to treatment with tetracycline.

Erythema Chronicum Migrans↗

Extramammary Paget's disease with aggressive behavior: a report of two cases.

Extramammary Paget's disease (EMPD) is an intraepithelial neoplastic disorder which is included as a rare malignant condition. However, it sometimes shows aggressive behavior of local recurrence and coexisting malignancy. We had experienced nine cases of EMPD involving the scrotum for seven years. Two cases of them presented metastasis. The first case presented extensive inguinal lymph node metastasis with underlying adnexal adenocarcinoma one year after wide local excision. The second case initially presented multiple metastasis to the liver and in the lymph node. The latter, showing fulminant progression with liver metastasis, may be only the second case reported in English literature. EMPD is considered as a malignant neoplasm with aggressive behavior from initial presentation. Because wide local excision of the lesion alone may be occasionally insufficient, a careful follow-up must be done to detect recurrence or internal malignancy.

Aged↗

Use of illicit drugs among high-school students in Jamaica.

Reported are the results of a survey to assess the prevalence of illicit drug use among high-school students in Jamaica. A total of 2417 high-school students in 26 schools were covered: 1063 boys and 1354 girls of whom 1317 were grade-10 students (mean age 15.7 years) and 1100 were grade-11 students (mean age 16.8 years). Of the students, 1072 and 1345 were from rural and urban schools, respectively, while 1126 and 1291 were children of parents who were professionals and nonprofessionals, respectively. The following drugs were used by the students: marijuana (10.2%), cocaine (2.2%), heroin (1.5%) and opium (1.2%). Illicit drug use among males, urban students and children of professionals was higher than that among females, rural students and children of nonprofessionals, respectively.

Adolescent↗

Pharmacokinetic changes of a new carbapenem, DA-1131, after intravenous administration to spontaneously hypertensive rats and deoxycorticosterone acetate-salt-induced hypertensive rats.

The pharmacokinetics of a new carbapenem, DA-1131, were compared after i.v. administration of the drug, 50 mg/kg, to spontaneously hypertensive rats (SHRs) at 16 weeks of age (an animal model for human primary hypertension) and at 6 weeks of age (corresponding to the early phase of the development of hypertension, at which time blood pressure remains within the normotensive range) and their respective age-matched control normotensive Kyoto-Wistar rats (KW rats), and deoxycorticosterone acetate-salt-induced hypertensive rats at 16 weeks of age (an animal model for human secondary hypertension) and their age-matched control Sprague-Dawley rats. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) (4720 versus 7070 microg x min/ml) was significantly smaller, and the nonrenal clearance (CLNR) (5.37 versus 3.57 ml/min/kg) was significantly faster in 16-week-old SHRs than those in their control KW rats. Similar results were also obtained from 6-week-old SHRs in AUC (3800 versus 4680 microg x min/ml) and CLNR (7.73 versus 3.31 ml/min/kg). However, the values were reversed in 16-week-old deoxycorticosterone acetate-salt rats in AUC (5310 versus 3870 microg.min/ml) and CLNR (2.57 versus 4.90 ml/min/kg). The significantly faster CLNR of DA-1131 in both 6- and 16-week-old SHRs could be supported at least partly by the results of the in vitro metabolism with kidney homogenate and considerably greater total renal dehydropeptidase-I activity. The data above indicated that the significantly faster CLNR of DA-1131 in 16-week-old SHRs than that in their age-matched control KW rats was due to any hereditary characteristics of SHRs and was not due to the hypertensive state itself.

Animals↗

Determination of a new naphthoquinone derivative, NQ12, in human plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of a new phospholipase A2 inhibitor, NQ12, in human plasma and urine. The sample preparation was simple: 2 volumes of acetonitrile were added to the biological samples to deproteinize it. A 50-microl aliquot of the supernatant was injected onto a C18 reversed-phase column. The mobile phase employed was 0.05M acetate buffer (pH 3) : acetonitrile : methanol (30:45:25, v/v/v) and run at a flow rate of 1.5 ml/min. The column effluent was monitored by a UV detector set at 298 nm. The retention times for NQ12 and the internal standard were approximately 5.5 and 7.0 min, respectively. The detection limits for NQ12 in human plasma and urine were all 20 ng/ml. The coefficients of variation of the assay (within-day and between-day) were generally low (below 11.8%) for human plasma and urine. No interferences from endogenous substances were found.

Chromatography, High Pressure Liquid↗

Enhanced absorption of oral furosemide by bile juice in rats.

The effect of bile juice on gastrointestinal absorption of furosemide was investigated in rats. Furosemide intravenous solution (Lasix), 20 mg/kg, was administered orally with (n = 5) or without (n = 6) bile juice administration after bile duct cannulation. With bile juice administration, the plasma concentrations of furosemide were considerably higher and AUC(0-8) h was significantly greater (2570 versus 658 microg x min/ml) suggesting that absorption of furosemide increased significantly by bile juice. This was supported by significantly smaller in the percentages of oral dose of furosemide recovered from entire gastrointestinal tract at 24 h: the values were 29.5% and 58.0% with and without bile juice administration, respectively.

Administration, Oral↗