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Biomedical subjects

M Kim

Publications and source records attributed to M Kim.

At least 181 records · Page 10Linked to original sources

Evaluation of 99mTc-mercaptoacetyltriglycine-biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin.

We evaluated 99mTc-labeled mercaptoacetyltriglycine (99mTc-MAG3)-biocytin as a hepatobiliary imaging agent in the absence and presence of bilirubin in mice. We then compared its pharmacokinetic parameters; peak liver/heart activity ratio (rmax) and half clearance time (HCT) with those of 99mTc-labeled diisopropyl-iminodiacetic acid (99mTc-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent (99mTc-MAG3-biocytin or 99mTc-disofenin) alone or in combination with bilirubin at two doses (7 and 14 mg/kg) dissolved in 5% human serum albumin. Images were acquired every 15 s for 30 min with a gamma-camera equipped with a pinhole collimator. Dynamic images showed rapid hepatic uptake of 99mTc-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its hepatic uptake was not affected by bilirubin coinjection, whereas 99mTc-disofenin coinjected with bilirubin showed a higher blood background than 99mTc-disofenin alone. These qualitative findings were reflected in pharmacokinetic parameters, rmax and HCT. The rmax was obtained from plots of time versus liver/heart activity ratios obtained in equal-area regions of interest over the heart and liver. The HCT was calculated from the hepatic clearance curve from plots of time versus liver activity. 99mTc-MAG3-biocytin without bilirubin coinjection showed an rmax of 8.9+/-1.3 and an HCT of 399+/-36 s. These values did not change even when 14 mg/kg of bilirubin were coinjected. By contrast, the parameters for 99mTc-disofenin with bilirubin were significantly (p < 0.01) affected by 14 mg/kg of bilirubin coinjection: rmax was decreased from 7.9+/-2.5 to 1.4+/-0.2 and HCT was increased from 292+/-32 s to 782+/-133 s. 99mTc-MAG3-biocytin hepatobiliary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic function in patients with high bilirubin levels.

Animals↗

Effect of heat shock on the vascular contractility in isolated rat aorta.

Stresses such as heat shock, ischemia, and irradiation have been known to induce heat shock proteins in various tissues. We investigated the effects of heat shock on the vascular contractility by using isolated rat aorta. Rat thoracic aortic rings were mounted in an organ bath maintained at 37 degrees C. For heat shock, aortic ring preparations were exposed to 42 degrees C for either 15 or 45 min (heat shock group), whereas the control group was left at 37 degrees C. Eight hours after heat shock, aortic ring preparations were subjected to contractions with high K(+) membrane-depolarizing solution. After functional study, tissues were frozen for measurement of heat shock protein 70 (HSP70). Heat shock not only increased the expression of HSP70 in the rat aorta, but also augmented contractions to KCl whether endothelium was present or denuded. Short exposure of tissues to 42 degrees C for 15 min did not work either. These results suggest that heat shock increases vascular contractility in isolated aortic strips.

Animals↗

Purification and characterization of N-Acetylglucosamine 6-phosphate deacetylase from Thermus caldophilus.

N-Acetylglucosamine 6-phosphate deacetylase [EC 3.5.1.25] was purified and biochemically characterized from an extreme thermophile, Thermus caldophilus GK24. The optimum temperature and pH of the enzyme were 80 degrees C and 7.5, respectively. The enzyme is a tetramer composed of identical 45 kDa subunits. The N-terminal amino acid sequence of the purified enzyme was determined to be MSVDLKTLHRRHVLTP. It hydrolyzed GlcNAc-6-P, but not GlcNAc-1-P or chitin oligosaccharides. The deacetylase activity was completely inhibited by the addition of 1 mM Cu2+, but moderately activated by that of 1 mM Mn2+ and Co2+. Within 2 h of reaction, 2 mM GlcNAc-6-P was completely hydrolyzed to GlcN-6-P and acetate by the action of the deacetylase.

Journal Article↗

Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans.

The effect of green tea catechin supplementation on antioxidant capacity of human plasma was investigated. Eighteen healthy male volunteers who orally ingested green tea extract (254 mg of total catechins/subject) showed 267 pmol of epigallocatechin-3-gallate (EGCg) per milliliter of plasma at 60 min after administration. The plasma phosphatidylcholine hydroperoxide (PCOOH) levels attenuated from 73.7 pmol/mL in the control to 44.6 pmol/mL in catechin-treated subjects, being correlated inversely with the increase in plasma EGCg level. The results suggested that drinking green tea contributes to prevent cardiovascular disease by increasing plasma antioxidant capacity in humans.

Adult↗

Intracranial involvement by metastatic advanced gastric carcinoma.

From a cohort of 8,080 patients with advanced gastric carcinoma (AGC), 13 patients who developed intracranial metastasis were evaluated retrospectively. The average age of onset of these patients was younger than that of remaining patients who did not appear to have intracranial metastasis. Five of these patients presented with leptomeningeal metastasis (LM) while the remaining 8 presented with parenchymal metastasis (PM). Five of 8 patients with PM had received operation and additional chemotherapy for primary cancer whereas one of five patients had received both treatments, who later developed LM. The mean interval between the diagnosis of AGC and intracranial metastasis was shorter in LM than that in PM. Neither chemotherapy nor radiation directed at the intracranial metastatic site altered the clinical course.

Adult↗

A system for the propagation of adenoviral vectors with genetically modified receptor specificities.

The development of genetically modified adenovirus (Ad) vectors with specificity for a single cell type will require both the introduction of novel tropism determinants and the ablation of endogenous tropism. Consequently, it will not be possible to exploit the native cellular entry pathway in the propagation of these targeted Ad vectors. Based on the concept that Ad enters cells by a two-step process in which a primary receptor serves as a high affinity binding site for the Ad fiber knob, with subsequent internalization mediated by alpha v integrins, we designed two artificial primary receptors. The extracellular domain of one of these synthetic receptors was derived from a single-chain antibody (sFv) with specificity for Ad5 knob, while the second receptor consisted of an icosapeptide identified by biopanning a phage display library against Ad5 knob. Expression of either of these artificial virus-binding receptors in fiber receptor-negative cells possessing alpha v integrins conferred susceptibility to Ad infection. We then created a novel mechanism for cell binding by genetically modifying both the vector and the target cell. In this approach, six histidine (His) residues were incorporated at the C-terminal of the Ad fiber protein. The resultant Ad vector was able to infect nonpermissive cells displaying the cognate artificial receptor, containing an anti-His sFv. This strategy, comprising a genetically engineered Ad virion and a modified cell line, should be useful in the propagation of targeted Ad vectors that lack the ability to bind the native fiber receptor.

Adenoviridae↗

A novel adenoviral vector expressing human Fas/CD95/APO-1 enhances p53-mediated apoptosis.

Recent evidence suggests an intriguing link between p53 and the Fas pathway. To evaluate this association further, we utilized a recombinant adenoviral vector (AdWTp53) to overexpress wild-type p53 in lung cancer (A549, H23, EKVX and HOP92) and breast cancer (MDA-MB-231 and MCF-7) cell lines and observed an increase in the Fas/CD95/APO-1 protein levels. Furthermore, this increase correlated with the sensitivity of the cell lines to p53-mediated cytotoxicity. To examine the effects of Fas over-expression in cells resistant to p53 over-expression, we constructed AdFas, an adenoviral vector capable of transferring functional human Fas to cancer cells. Interestingly, infection of p53-resistant MCF-7 cells with AdFas sensitized them to p53-mediated apoptosis. These studies indicate that combined over-expression of Fas and wild-type p53 may be an effective cancer gene therapy approach, especially in cells relatively resistant to p53 over-expression.

Adenoviridae↗

Solid-phase microextraction for the determination of pethidine and methadone in human urine using gas chromatography with nitrogen-phosphorus detection.

A simple and rapid analytical method is presented for the determination of pethidine (meperidine) and methadone in human urine using solid-phase microextraction (SPME) and gas chromatography with nitrogen-phosphorus detection (GC-NPD). After the analytes had been partitioned between an extracting phase and the aqueous sample matrix, the needle of the coating fiber assembly was injected directly into the GC injector. The analytes were thermally desorbed in the heated injector (240 degrees C) and subsequently separated and detected by the GC-NPD system. The factors influencing the SPME method, such as the salt (NaCl) effect (15%), pH (pH 11), and equilibration time (30 min), were optimized. The calibration graphs for urine samples showed a good linearity. The detection limit was below 1 ng ml-1 for both drugs.

Chromatography, Gas↗

In vivo analysis of plastid psbA, rbcL and rpl32 UTR elements by chloroplast transformation: tobacco plastid gene expression is controlled by modulation of transcript levels and translation efficiency

5' and 3' untranslated regions (UTRs) of plastid RNAs act as regulatory elements for post-transcriptional control of gene expression. Polyethylene glycol-mediated plastid transformation with UTR-GUS reporter gene fusions was used to study the function of the psbA, rbcL and rpl32 UTRs in vivo. All gene fusions were expressed from the same promoter, i.e. the promoter of the 16S-rRNA gene, such that variations in RNA and protein levels would be due to the involved UTR elements alone. Transgenic tobacco lines containing different combinations of UTRs showed fivefold variation in the uidA-mRNA level (RNA stability) and approximately 100-fold differences in GUS activity, a measure of translation activity. The rbcL 5'-UTR conferred greater mRNA stability than the psbA 5'-UTR on uidA transcripts. In contrast, the psbA 5'-UTR enhanced translation of GUS to a much greater extent compared to the rbcL 5'-UTR. The psbA 5'-UTR also mediated light-induced activation of translation which was not observed with other constructs. Deletion mutagenesis of an unanalysed terminal sequence element of the psbA 5'-UTR resulted in a twofold drop in uidA-mRNA level and a fourfold decrease in translation efficiency. Exchange of 3'-UTRs results in up to fivefold changes of mRNA levels and does not significantly influence translation efficiency. The mechanical impacts of these results on plastid translation regulation are discussed.

Journal Article↗

Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure.

BACKGROUND: In patients with chronic renal failure (CRF), abnormalities in vitamin D metabolism are known to be present, and several factors could contribute to the abnormalities. METHODS: We measured serum levels of three vitamin D metabolites, 1,25(OH)2D, 24, 25(OH)2D and 25(OH)D, and analyzed factors affecting their levels in 76 nondialyzed patients with CRF (serum creatinine> 1.6 and < 9.0 mg/dl), 37 of whom had diabetes mellitus (DM-CRF) and 39 of whom were nondiabetic (nonDM-CRF). RESULTS: Serum levels of 1,25(OH)2D were positively correlated with estimated creatinine clearance (CCr; r = 0.429; P < 0.0001), and levels of 24,25(OH)2D were weakly correlated with CCr (r = 0.252, P < 0.05); no correlation was noted for 25(OH)D. Serum levels of all three vitamin D metabolites were significantly and positively correlated with serum albumin. Although there were no significant differences in age, sex, estimated CCr, calcium and phosphate between DM-CRF and nonDM-CRF, all three vitamin D metabolites were significantly lower in DM-CRF than in nonDM-CRF. To analyze factors influencing vitamin D metabolite levels, we performed multiple regression analyses. Serum 25(OH)D levels were significantly and independently associated with serum albumin, presence of DM and serum phosphate (R2 = 0.599; P < 0.0001). 24,25(OH)2D levels were significantly and strongly associated with 25(OH)D (beta = 0.772; R2 = 0.446; P < 0.0001). Serum 1,25(OH)2D levels were significantly associated only with estimated CCr (R2 = 0. 409; P < 0.0001). CONCLUSIONS: These results suggest that hypoalbuminemia and the presence of DM independently affect serum 25(OH)D levels, probably via diabetic nephropathy and poor nutritional status associated with diabetes, and that 25(OH)D is actively catalyzed to 24,25(OH)2D in CRF, probably largely via extrarenal 24-hydroxylase. Serum levels of 1,25(OH)2D were significantly affected by the degree of renal failure. Thus, this study indicates that patients with CRF, particularly those with DM, should receive supplements containing the active form of vitamin D prior to dialysis.

24,25-Dihydroxyvitamin D 3↗

Barbarin as a new tyrosinase inhibitor from Barbarea orthocerus.

A tyrosinase inhibitor was isolated from the whole plant of Barbarea orthocerus Led. (Brassicaceae) by activity-guided fractionation, and identified as (R)-5-phenyl-2-oxazolidinethione (barbarin) by structural analysis followed by comparison with reported spectral data. The compound exhibited significant inhibitory effects on mushroom and murine tyrosinases at more than 1.6 x 10(-5) M. Barbarin exhibited IC50 values of 4.2 x 10(-5) M on mushroom tyrosinase and of 4.8 x 10(-5) M on murine tyrosinase. Kojic acid as a positive control exhibited IC50 values of 3.4 x 10(-5) M and 6.0 x 10(-5) M on mushroom and murine tyrosinases, respectively. Therefore, barbarin exhibited a similar level of inhibitory potency with kojic acid used as a positive control. In a kinetic study with various concentrations of L-dopa as the substrate, barbarin was identified as an uncompetitive inhibitor and kojic acid as a mixed inhibitor of both mushroom and murine tyrosinases. Barbarin exhibited KEIS values of 3.3 x 10(-5) M and 3.6 x 10(-5) M on mushroom and murine tyrosinases, respectively. Kojic acid exhibited KEIS and KEI values of 2.4 x 10(-5) M and 2.2 x 10(-5) M on mushroom tyrosinase and those of 8.9 x 10(-5) M and 7.2 x 10(-5) M on murine tyrosinase, respectively.

Animals↗

Differential regulation of transcription termination occurring at two different sites on the micro-delta gene complex.

The progression of polymerases across the micro-delta Ig heavy chain gene complex is characterized by two termination events occurring at different sites on the transcription unit and at different times during B cell differentiation. We have utilized two mouse strains to analyze the regulatory determinants for these events in primary B cells. In the transgenic pmicro.microdeltaRatt strain a 1160 bp intervening DNA segment (the att site) has been inverted. This mutation results in the abrogation of transcription termination that occurs in early B cells. Using a novel method that takes advantage of an internal ribosome entry site we have further restricted the size of the segment that is needed for inducing transcription termination in transfectants. This 200 bp termination-inducing sequence operates in tumor equivalents of early but not mature B cells and the activity is correlated with differential binding of nuclear proteins. To explore the regulatory basis for the change in site of transcription termination upon B cell activation we have examined the microS-/- deletion mutant strain in which the microS poly(A) site has been eliminated. The results suggest that polyadenylation at the microS site plays a dominant but not exclusive role in regulating transcription termination in activated B cells.

Animals↗

ADP-Dependent phosphorylation regulates association of a DNA-binding complex with the barley chloroplast psbD blue-light-responsive promoter.

The chloroplast gene psbD encodes D2, a chlorophyll-binding protein located in the photosystem II reaction center. Transcription of psbD in higher plants involves at least three promoters, one of which is regulated by blue light. The psbD blue-light-regulated promoter (BLRP) consists of a -10 promoter element and an activating complex, AGF, that binds immediately upstream of -35. A second sequence-specific DNA-binding complex, PGTF, binds upstream of AGF between -71 and -100 in the barley (Hordeum vulgare) psbD BLRP. In this study we report that ADP-dependent phosphorylation selectively inhibits the binding of PGTF to the barley psbD BLRP. ATP at high concentrations (1-5 mM) inhibits PGTF binding, but in the presence of phosphocreatine and phosphocreatine kinase, this capacity is lost, presumably due to scavenging of ADP. ADP inhibits PGTF binding at relatively low concentrations (0.1 mM), whereas other nucleotides are unable to mediate this response. ADP-mediated inhibition of PGTF binding is reduced in the presence of the protein kinase inhibitor K252a. This and other results suggest that ADP-dependent phosphorylation of PGTF (or some associated protein) inhibits binding of PGTF to the psbD BLRP and reduces transcription. ADP-dependent phosphorylation is expected to increase in darkness in parallel with the rise in ADP levels in chloroplasts. ADP-dependent phosphorylation in chloroplasts may, therefore, in coordination, inactivate enzymes involved in carbon assimilation, protein synthesis, and transcription during diurnal light/dark cycles.

Adenosine Diphosphate↗

Extracorporeal photochemotherapy for cutaneous T-cell lymphoma: a 9.7-year experience.

Cutaneous T-cell lymphoma (CTCL) is an indolent lymphoma usually of CD4+ T lymphocytes in which the aggressive treatment for the advanced stages does not increase survival. Photopheresis has been established as an alternative modality for the therapy of erythrodermic CTCL and reportedly improves survival in patients with advanced stages of the disease. The objective of this study is to review the experience of treating patients with erythrodermic CTCL with extracorporeal photochemotherapy (ECP) at the New York Veteran Affairs Medical Center/NYU Medical Center between September 1987 and April 1997. Forty-one patients with erythrodermic CTCL (stages III and IV) received photopheresis; 25 of them fulfilled the inclusion criterion, i.e., the completion of greater than or equal to 6 cycles of photopheresis. Skin score was defined as a product of severity and percentage of involved surface area. Complete clinical response was defined as disappearance of measurable disease for at least one month, and partial response was defined as greater than or equal to 50% clearance of measurable disease for at least one month. The profile of the patients was: 20 men, 5 women; average age: 64.2 years; 17 patients had stage III disease, and 8 had stage IV disease. Five of the 25 patients (20%) achieved complete clinical response, another 15 (60%) had partial response, and 5 (20%) had no response. The mean time (+/- SD) to achieve complete clinical clearance was 12.6 +/- 10 months (range: 4-30 months) and the mean time (+/- SD) to obtain partial clinical response, including complete response, was 9.7 +/- 5.3 months (range: 4-17 months). Remission duration ranged from 9 to 67 months. The median survival time from the time of initiation of photopheresis is estimated at 70 months. The complete responder group had a lower median CD4/CD8 ratio compared to the non-responders at baseline (3.8 vs 7.2, respectively), although the difference was not statistically significant (P = 0.40). At the time of maximal response, the CD4/CD8 ratio of the complete responder group decreased towards normal values (median = 1.2), whereas this ratio increased among the non-responders (median = 11.0; P = 0.04). Side effects were minimal. Extracorporeal photochemotherapy is an effective and safe treatment for erythrodermic CTCL. In some of these patients, it can induce a long-term and complete clinical remission.

Female↗

Ipsilesional neglect: behavioural and anatomical features.

OBJECTIVE: To learn more about the behavioural and anatomical features of ipsilesional neglect. METHODS: Thirty consecutive patients with spatial neglect were tested on cancellation and line bisection tasks. To learn if patients with ipsilesional neglect demonstrate the sensory-attentional or motor-intentional type of neglect, a video apparatus was used that dissociates these determinants. RESULTS: Five patients showed evidence of ipsilesional neglect. This phenomenon was seen only on the line bisection task. All patients with ipsilesional neglect had lesions involving frontal-subcortical regions. Although ipsilesional neglect evolved from early in three of five cases, the other patients displayed ipsilesional neglect without initial contralateral neglect, suggesting that ipsilesional neglect cannot be fully attributed to a compensatory strategy. The results of the tests that used the video apparatus indicate that right sided frontal or subcortical injury may induce contralateral attentional or intentional "approach" behaviours. CONCLUSIONS: Ipsilesional neglect is most often associated with frontal-subcortical lesions, cannot be entirely attributed to a compensatory strategy, and may be induced by an attentional bias, an intentional bias, or both.

Adult↗

Pupillographic findings in neglect.

OBJECTIVES: Unilateral sensory neglect has been attributed to various defects, including a hemispatial attention-arousal deficit. However, support for this hypothesis has only been indirect. Therefore, the purpose of this study was to further test the hemispatial attentional-arousal hypothesis by measuring pupillary response as an index of arousal. METHODS: There were two experimental subjects with neglect and six matched controls. Stimuli (Arabic numbers) were presented on the right, left, and centre of a screen. The subjects were asked to look at the number in the centre, on the right, or left of the screen while their pupil diameter was measured. RESULTS: Unlike the control subjects, the subjects with neglect, who were aware of the left sided stimuli, did not show a pupillary dilatation when they looked at the stimulus on the left. CONCLUSIONS: Although this study provides support for the hemispatial attention-arousal hypotheses of neglect, it does not preclude the possibility that other mechanisms may also be important.

Aged↗

Choledochal cyst associated with polycystic kidney disease: report of a case.

We report a very rare case of type I choledochal cyst associated with a polycystic kidney disease. A 48-year-old female had been dependent on hemodialysis for chronic renal failure due to polycystic kidney disease and was incidentally diagnosed to have a dilated common bile duct by an ultrasonography. An endoscopic retrograde cholangiopancreatography showed a spindle-shaped, dilated common bile duct (type I choledochal cyst) without visualization of the pancreatic duct. She underwent a resection of the choledochal cyst. Intraoperative cholangiography showed no reflux of contrast medium into the pancreatic duct. Amylase level of the aspirated bile from the bile duct was not elevated. In the case of choledochal cyst combined with renal fibropolycystic disease, pancreaticobiliary maljunction may not contribute to the etiology of choledochal cyst. In such cases, management of choledochal cyst is still controversial and requires further discussion.

Cholangiopancreatography, Endoscopic Retrograde↗

The treatment of attention-deficit hyperactivity disorder: an annotated bibliography and critical appraisal of published systematic reviews and metaanalyses.

CONTEXT: The Agency for Health Care Policy and Research charged the McMaster Evidence-based Practice Center with conducting a comprehensive systematic review of the literature on the treatment of attention-deficit hyperactivity disorder (ADHD), with input from various groups of stakeholders. One strategy used to avoid duplication of work included a critical appraisal of existing systematic reviews and metaanalyses. OBJECTIVE: To identify and appraise published metaanalyses and systematic reviews on the treatment of ADHD and to produce an annotated bibliography. DATA SOURCES: Medline, Cumulative Index in Nursing and Allied Health (CINAHL), Healthstar, Psycinfo, and Embase were searched to September 1998; the Cochrane Database (1998 issue 3), selected Internet sites, and the files of investigators were also reviewed. STUDY SELECTION: Review articles described as systematic reviews or metaanalyses or including a Methods section were identified independently by 3 reviewers. DATA EXTRACTION: Two reviewers extracted, by consensus, relevant information on the name, methodological quality, ADHD-related aspects (comorbid disorders, family characteristics) of those reviews; data on the population, study setting, interventions, and outcomes evaluated by the reviews were also retrieved. RESULTS: Thirteen reviews, published from 1982 to 1998, were included. Eight included metaanalysis and 5 a qualitative review. Nonpharmacological treatments were mentioned in 6 reviews and combination therapies in 3. One review focused on the treatment of adults. Forty-seven drugs and 20 adverse effects were mentioned. Most reviews had major methodological flaws. CONCLUSIONS: Most published systematic reviews and metaanalyses on the treatment of ADHD have limited value for guiding clinical, policy, and research decisions. A rigorous, systematic review following established methodological criteria is warranted.

Attention Deficit Disorder with Hyperactivity↗