Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 1,045 records · Page 58Linked to original sources

PubMed1993

Useful components of the shunt tap test for evaluation of shunt malfunction.

Results of shunt tap were studied in 224 clinically or radiologically suspected instances of shunt malfunction. In 130 retrospectively studied patients the results of the tap had reported the opening pressure and ease of aspiration. In 94 prospectively studied instances the shunt tap parameters described were (i) the opening pressure, (ii) the drip interval, i.e., the interval between the drops of cerebrospinal fluid when the open end of the butterfly used for tapping was placed 5 cm below the level of the valve, and (iii) the closing pressure. The efficacy of the aspiration procedure for proximal malfunction was 40.3%, compared with the efficacy of drip interval which was 95.1%. For distal malfunction, the efficacy of measurement of opening pressure was 54.3% whereas that of closing pressure was 60.6%. An in vitro model of a functioning shunt showed that the opening and the closing pressures were related to the flow rate and the level of the distal catheter tip with respect to the valve, whereas the drip interval was linearly related to the flow through the proximal catheter and was independent of the distal catheter position. The opening pressure, closing pressure, and the drip interval recorded at surgery were not significantly different from the values obtained by shunt tap. The results suggested that shunt tap accurately provides information otherwise obtained at surgery and the drip interval is most useful for evaluating a proximal malfunction. The subjective impression of the distal flow may be more helpful in diagnosing distal malfunction rather than the absolute level of opening or closing pressures.

Cerebrospinal Fluid Pressure↗

PubMed1993

Time course of the changes in prednisolone pharmacokinetics after co-administration or discontinuation of rifampin.

We have investigated changes in the pharmacokinetics of prednisolone caused by co-administration or discontinuation of rifampin. Serial IV pharmacokinetic studies of prednisolone (1 mg/kg) in groups of 3 patients over a 1 month period of rifampin co-treatment or after its withdrawal, revealed significant changes in the area under the curve, the total clearance, the non-renal clearance and the half-life. The changes in the pharmacokinetic parameters reached a 1.5 to 2-fold plateau after 2 weeks and the half maximal effect was attained within 5 days. Neither the volume of distribution nor the protein binding of prednisolone were significantly altered.

Adult↗

PubMed1993

A slow-release methotrexate formulation for intrathecal chemotherapy.

Optimal anticancer treatment with cell cycle phase-specific antimetabolites requires a sustained maintenance of cytotoxic drug levels. However, drugs that can be administered intrathecally have short half-lives in cerebrospinal fluid (CSF) and require repeated administrations by lumbar punctures, which are painful and inconvenient. Implantable pumps are expensive and require surgery. In a rat model, a lipid-based formulation of methotrexate (Depo/methotrexate) was tested for extended maintenance of therapeutic CSF concentration after a single injection. The half-life of methotrexate in CSF after an intracisternal injection of Depo/methotrexate was 5.4 days compared to 0.30 days for unencapsulated methotrexate. This 18-fold increase in methotrexate half-life may make Depo/methotrexate useful for intrathecal chemotherapy of neoplastic meningitis.

Animals↗

PubMed1993

Extended-release formulation of morphine for subcutaneous administration.

Pain arising from cancer tends to be chronic and chemotherapy of cancer pain usually requires narcotics. Most injectable narcotics, however, have short half-lives (T1/2) and require either continuous infusion or repeated frequent injections which are both inconvenient and uncomfortable. An extended-release formulation of morphine sulfate (Depo/Morphine) in a lipid-based drug-delivery system was characterized and tested in an animal model. The encapsulation efficiency was 53% +/- 4%, and the in vitro release T1/2 in human plasma at 37 degrees C was 12.1 +/- 1.1 days. Following s.c. administration of Depo/Morphine, the total amount of morphine remaining at the s.c. injection site decreased monoexponentially with a T1/2 value of 2.59 +/- 0.16 days as compared with 0.46 +/- 0.04 h following the injection of unencapsulated morphine. The morphine concentration in plasma also decreased monoexponentially with a T1/2 value of 8.33 +/- 2.13 days as compared with 0.45 +/- 0.21 h for unencapsulated morphine. Cataleptic behavior was observed in mice injected with unencapsulated morphine but not in those given an identical dose of morphine in the form of Depo/Morphine. In conclusion, Depo/Morphine has potential as an extended-release formulation of morphine and may be useful in chemotherapy of cancer pain as well as in maintenance therapy of narcotic addicts.

Animals↗

PubMed1993

Pharmacokinetics of an extended-release human interferon alpha-2b formulation.

The in vivo half-life of human interferon alpha-2b (hIFN-alpha-2b) is relatively short, and frequent injections over prolonged periods are required for efficacy. An extended-release formulation of hIFN-alpha-2b (Depo/IFN) was created by encapsulation into a lipid-based drug-delivery system. The capture efficiency was 51% +/- 13% and the release half-life in human plasma at 37 degrees C was 16 days. The pharmacokinetics of Depo/IFN was compared with that of unencapsulated standard hIFN-alpha-2b (Std/IFN) in the peritoneal cavity of male BDF1 mice. Depo/IFN exhibited a 13-fold longer intraperitoneal (i.p.) half-life as compared with Std/IFN (20 vs 1.5 h). The release of free hIFN-alpha-2b from Depo/IFN into the peritoneal cavity was slow and protracted, with a 10-fold lower peak concentration and a 13-fold longer apparent half-life being observed in comparison with Std/IFN. The areas under the curve of free hIFN-alpha-2b in the peritoneal cavity were comparable for Depo/IFN and Std/IFN. hIFN-alpha-2b was detectable in plasma only after the i.p. administration of Std/IFN. These data suggest the possibility that Depo/IFN may be useful as an extended-release formulation of hIFN-alpha-2b.

Animals↗

PubMed1993

Comparative studies on S-adenosyl-L-methionine binding sites of protein N-methyltransferases, using 8-azido-S-adenosyl-L-methionine as photoaffinity probe.

Employing a photoaffinity labeling procedure with 8-azido-S-adenosyl-L-[methyl-3H]methionine (8-N3-Ado[methyl-3H]Met), the binding sites for S-adenosyl-L-methionine(AdoMet) of three protein N-methyltransferases [AdoMet:myelin basic protein-arginine N-methyltransferase (EC 2.1.1.23); AdoMet:histone-arginine N-methyltransferase (EC2.1.1.23); and AdoMet:cytochrome c-lysine N-methyltransferase (EC2.1.1.59)] have been investigated. The incorporation of the photoaffinity label into the enzymes upon UV irradiation was highly specific. In order to define the AdoMet binding sites, the photolabeled enzymes were sequentially digested with trypsin, chymotrypsin, and endoproteinase Glu-C. After each proteolytic digestion, radiolabeled peptide from each enzyme was resolved on HPLC first by gradient elution and further purified by an isocratic elution. Retention times of the purified radiolabeled peptides from the three enzymes from the corresponding proteolysis were significantly different, indicating that their sizes and compositions were different. Amino acid composition analysis of these peptides confirmed further that the AdoMet binding sites of these protein N-methyltransferases are quite different.

Affinity Labels↗

PubMed1993

Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett's epithelium.

Metaplastic columnar epithelium replaces the normal squamous epithelium in Barrett's esophagus. We characterized the surface epithelial cells of the junction between squamous and Barrett's epithelium using scanning electron microscopy and light microscopy. In four biopsy specimens from the squamous-Barrett's junction in three patients, we found a distinctive cell type having features intermediate between those of squamous and columnar epithelium. Its distinguishing characteristic is the presence on its surface of two disparate structures not normally present on the same cell in the gastrointestinal tract: microvilli (a scanning electron microscopy feature of glandular epithelium) and intercellular ridges (a scanning electron microscopy feature of squamous mucosa). The surface characteristics of this newly recognized cell were strikingly similar to those of cells found in the transformation zone of the uterine cervix, an area in which squamous epithelium physiologically replaces columnar epithelium. We also examined 28 biopsies of the gastroesophageal junction area from 14 patients with and without a history of heartburn but with no evidence of Barrett's esophagus. None of these biopsies showed the distinctive cell. We hypothesize that this distinctive cell represents an intermediate step in either the development or the healing of Barrett's epithelium, during which surface characteristics of two different cell types, columnar and squamous, coexist on the same cell.

Aged↗

PubMed1993

A peptide inhibitor for S-adenosyl-L-methionine-dependent transmethylation reactions. Purification and characterization.

1. A. proteinaceous inhibitor for S-adenosyl-L-methionine (AdoMet)-dependent transmethylation reactions has been purified to apparent homogeneity from rat liver cytosolic fraction. 2. The peptide was made up of 29 amino acid residues with a molecular weight of 2,584. Glycine accounted for 52% of the total amino acids. 3. Employing AdoMet: protein-carboxyl O-methyltransferase (Protein methylase II) and bovine serum gamma-globulin as in vitro substrate, the mode of inhibition was found to be non-competitive with Ki value of 1.9 x 10(-8) M. 4. When the inhibitor was present in the reaction mixture together with S-adenosyl-L-homocysteine (AdoHcy), which is a competitive inhibitor for AdoMet, the extent of inhibition exceeded that exerted by each individual inhibitor alone, suggesting that the sites of the inhibitors on the enzyme molecule are different. 5. Almost a stoichiometric relationship exists between the enzyme and the inhibitor molecule, the ratio being approx one.

Amino Acids↗

PubMed1993

Human complement factor B: cDNA cloning, nucleotide sequencing, phenotypic conversion by site-directed mutagenesis and expression.

A full-length cDNA clone, BHL4-1, encoding factor B was isolated from a human liver cDNA library and sequenced in its entirety. It consists of 2388 bp which include a 5'-untranslated region of 40 bp, a single open reading frame, 2292 bp in length, and a 3'-untranslated region of 56 bp followed by a poly-A tail. The deduced amino acid sequence comprises 25 residues of a putative leader peptide and 739 residues of the mature polypeptide chain of the F allele of factor B. We constructed an S allele-like Q7R mutant of BHL4-1 by site-directed mutagenesis. Both the wild-type and mutant factor B cDNA were expressed transiently in a eukaryotic system. The specific hemolytic activities of the two recombinant factor B alleles and of native B were not significantly different from each other.

Alleles↗

PubMed1993

Skin concentration of 8-methoxypsoralen, 5-methoxypsoralen and 4,5,8-trimethylpsoralen in guinea pigs.

The skin concentrations of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5,8-trimethylpsoralen (TMP) were studied in the albino guinea pig following oral administration and intraperitoneal injection. The skin concentration of phototoxic drugs after oral administration peaked at 1.5 h, and the concentration of 8-MOP was 3.5 times greater than that of 5-MOP. The skin concentration of TMP was not detected in our study (limit of sensitivity 5 ng/ml). The highest skin concentrations of 8-MOP and 5-MOP after intraperitoneal injection were achieved for both drugs at 0.5 h, with the level of 8-MOP approximately 1.3 times higher than that of 5-MOP. The level of TMP could not be measured even in the case of intraperitoneal injection.

5-Methoxypsoralen↗

PubMed1993

A phase I and pharmacokinetic study of intraperitoneal carboplatin and etoposide.

BACKGROUND: We attempted to determine the maximum tolerated dose and toxicity of etoposide (VP-16) when administered in combination with carboplatin (CBDCA) (300 mg m-2) and administered via the intraperitoneal (IP) route. METHODS AND MATERIALS: A total of 26 patients were treated on this trial. CBDCA was administered at a fixed dose of 300 mg m-2) while VP-16 was started at a dose of 200 mg m-2 and escalated at 50 mg m-2 increments. Both agents were mixed together in 2 litres of 5% Dextrose and administered as quickly as possible into the peritoneal cavity. Pharmacokinetic studies were performed at the maximum tolerated dose (MTD). RESULTS: The MTD for this regimen was CBDCA 300 mg m-2 and VP-16 350 mg m-2. Patients > or = 70 years of age or who had received more than six cycles of previous chemotherapy, tolerated this regimen poorly. The MTD for this group of patients was CBDCA 200 mg m-2 and VP-16 50 mg m-2. Neutropenia was the dose limiting toxicity for both groups. The mean peritoneal/plasma peak ratio was 18.3 for CBDCA and 12.7 for VP-16. The pharmacologic advantage (peritoneal/plasma AUC ratio) was 14.9 for CBDCA and 8.8 for VP-16. Although measurable disease was not a requirement for entrance into this study a response rate of 27% was noted in 15 patients with evaluable disease who had ovarian cancer. CONCLUSIONS: A pharmacologic advantage exists for both CBDCA and VP-16 when administered together via the IP route.

Adult↗

PubMed1993

Regulation of initial vinblastine influx by P-glycoprotein.

P-glycoprotein (PGP) is an energy-dependent efflux pump that serves to protect cells against the cytotoxicity of many natural product drugs including vinblastine (VBL). In this study we investigated the role of PGP in regulating initial VBL influx. The apparent influx of VBL, measured over the first 20 s, was 2-fold lower in KB-GRC1 cells expressing a transfected mdr1 gene at high level than in non-expressing parental KB-3-1 cells. Inhibition of PGP efflux function with dipyridamole increased the influx rate constant by 4.0-fold in the KB-GRC1 cells but only 2.1-fold in the KB-3-1 cells. Verapamil, another inhibitor of PGP-mediated efflux, increased the initial influx rate constant by 2.7-fold in the KB-GRC1 cells but only 1.4-fold in the KB-3-1 cells. Inhibition of PGP function by depletion of ATP increased influx by 6.8-fold and 2.2-fold in the two cell types, respectively. Mutation of PGP at both ATP binding sites abolished its ability to limit initial influx. Thus, VBL is serving as an efficient substrate for the efflux pump even within the first few seconds of drug exposure, consistent with the hypothesis that PGP may directly efflux drug from the cell membrane.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Decreased acetylation of isoniazid in chronic renal failure.

Pharmacokinetic parameters of isoniazid obtained from 37 normal subjects were compared with parameters obtained from 14 patients with chronic renal failure. In the 29 normal rapid acetylators and eight normal slow acetylators, the mean plasma half-life values of isoniazid were 1.54 +/- 0.31 and 3.68 +/- 0.59 hours, respectively. The plasma half-life values of isoniazid in patients with chronic renal failure varied widely from 1.30 to 10.13 hours, but the values were significantly longer than those of normal subjects. Because isoniazid clearance is governed mainly by hepatic metabolism, such a significant prolongation of plasma half-life of isoniazid was unexpected; thus the pharmacokinetics of isoniazid were reevaluated in the same patients with chronic renal failure after the kidney transplantation. After successful kidney transplantation, the shortening of isoniazid half-life was pronounced and the nonrenal clearance was markedly increased. These findings indicate that decreased isoniazid clearance in chronic renal failure is caused in minor part by the decreased renal excretion of isoniazid and in major part by the depressed hepatic N-acetylation of isoniazid.

Acetylation↗

PubMed1993

Biochemical characteristics of human renin expressed in transgenic mice.

1. Biochemical properties of human renin expressed in transgenic mice (hRN8-12 mice) carrying the human renin gene (Fukamizu et al. Biochem Biophys Res Commun 1989; 165: 826-32) were examined. The optimum pH of the enzymic activity against human angiotensinogen was 5.5 for both plasma and renal human renin in the hRN8-12 mice. Plasma concentrations of human active and inactive renin in the plasma of hRN8-12 mice were 16.7 +/- 2.8 and 79.9 +/- 14.0 pmol of angiotensin Ih-1 ml-1, respectively, thereby indicating that the predominant form of plasma human renin is the inactive form, as is the case in humans. 2. The molecular masses of plasma human active and inactive renin and renal human active renin in the hRN8-12 mice were estimated to be 46 kDa, 48 kDa and 44 kDa, respectively, as determined by h.p.l.c. on G3,000SW. 3. Human renin in the hRN8-12 mouse kidney was bound to a concanavalin A-Sepharose column, and was eluted with alpha-methyl-D-mannoside, showing that this renin is glycosylated, as is native human renin. 4. Low sodium treatment of the hRN8-12 mice for 2 weeks increased plasma human active renin, renal human renin and renal human renin mRNA levels by 2.6-, 3.8- and 2.8-fold, respectively. Thus, the biosynthesis and secretion of renal human renin in these transgenic mice are obviously stimulated by sodium depletion.

Animals↗

PubMed1993

Space-time accuracy of rapid movements.

The space-time accuracy of an elbow flexion movement task was examined in two experiments over a range of motion extents (1 degrees through 100 degrees ) and short-duration movement times (100, 125, 150, and 400 ms). Nonlinear speed-accuracy functions emerged for both spatial and temporal error over all the movement conditions examined. The results showed that the timing error and spatial error had a high degree of complementarity as predicted by a space-time model of the speed-accuracy relation (Hancock & Newell, 1985). The findings confirm that the frame of reference for measuring movement error determines in part the error functions observed.

Journal Article↗

PubMed1993

Localization of Hantaan viral envelope glycoproteins by monoclonal antibodies in renal tissues from patients with Korean hemorrhagic fever H.

The role of viruses in several renal diseases is not documented clearly. The authors attempted to localize envelope glycoproteins of Hantaan virus in biopsy specimens from patients with Korean hemorrhagic fever (KHF) as evidence of direct viral invasion of renal tissues. The authors studied sequential sections of kidney biopsy specimens from 23 of 35 patients with serologically confirmed KHF diagnosed between June 1985 and December 1989. The sections were stained with the avidin-biotin-peroxidase complex method with monoclonal antibodies to G1 and G2 envelope glycoproteins. Control antibodies of the same isotype were used to rule out nonspecific staining, and hyperimmune rabbit sera or convalescent sera of patients with KHF were used for blocking tests. Normal renal tissues and kidney biopsy tissues from minimal-change nephrotic syndrome were used as negative control sections. The kidney biopsies were performed between the fifth and thirtieth days after onset of fever. The authors detected viral glycoproteins in renal tissues from 22 of the 23 patients. The viral glycoproteins were localized in the cytoplasm of the tubular epithelial cells, and the distribution of viral glycoproteins in the tubules was focal. Glycoproteins also were localized in the cytoplasm of the sloughed renal tubular epithelial cells, where tubular degenerative changes were prominent. These findings suggest the direct invasion of renal tubules by the virus and may partly explain the pathogenesis of acute renal failure in KHF.

Adolescent↗

PubMed1993

Dose intensification of cisplatin chemotherapy through biweekly administration.

PURPOSE: Dose intensity (DI, expressed in mg/m2/wk) may be an important factor in the clinical use of cisplatin (DDP). We have explored the shortening of the cycle interval as a way to increase the DI of DDP. PATIENTS AND METHODS: DDP 180 mg/m2 was given intravenously (i.v.) over 4 hours; sodium thiosulfate (STS) was given i.v. in the opposite arm at a loading dose of 4 g/m2, followed by 12 g/m2 over 6 hours. Each cycle was repeated every two weeks. Seventy-five cycles were administered to 28 patients in this clinical trial. RESULTS: In 19 patients who received 2 or more cycles of chemotherapy, a delay of three or more days was required on 17/66 courses (26%); the mean DDP DI actually received by these patients was 83 mg/m2/wk (88% of the planned DI). The major side effect was ototoxicity; this occurred in 9 patients (33%), but none required a hearing aid. Myelosuppression was moderate with thrombocytopenia greater than neutropenia. Nephrotoxicity (creatinine > 2 mg/dl) occurred on only 2 cycles (3%). Three patients (11%) developed symptoms of peripheral neuropathy. In 23 evaluable patients, the overall response rate was 39%. CONCLUSION: It is feasible to give 180 mg/m2 of DDP and STS every two weeks with tolerable nephrotoxicity but without blocking other types of toxicity, such as myelosuppression and ototoxicity. The shortening of cycle intervals resulted in a markedly increased DI.

Adult↗

PubMed1993

Purification and characterization of flavine-adenine dinucleotide phosphohydrolase from rat liver lysosomal membranes.

An enzyme hydrolyzing flavine-adenine dinucleotide (FAD) to flavine mononucleotide (FMN) and adenosine monophosphate (AMP) was purified about 460-fold over the isolated lysosomal membranes with 9% recovery to apparent homogeneity, as determined from the pattern on polyacrylamide gel electrophoresis in the presence and the absence of SDS. Purification procedures included: preparation of crude lysosomal membranes, solubilization with Triton X-100, WGA-Sepharose, Con A-Sepharose, hydroxylapatite chromatography, gel filtration with Superdex 200, DEAE ion exchange chromatography, and preparative polyacrylamide gel electrophoresis. The molecular mass of the purified enzyme, estimated by gel filtration with Superdex 200, was approximately 560 kDa, and SDS-polyacrylamide gel electrophoresis showed the enzyme to be composed of four identical subunits with an apparent molecular weight of 140,000. The pH optimum for FAD hydrolysis was 8.5 with an apparent Km of 0.1 mM and the isoelectric point was pH 7.3. The activity was inhibited by o-phenanthroline, EDTA, DTT, and NEM and was slightly stimulated by Zn ion, but was not affected by Ca or Mg ions. The purified FADase contained N-linked complex type oligosaccharide chains lacking neuraminic acids. The NH2 terminal 21 amino acid residues of the purified FADase were Ser-Pro-Cys-Val-Cys-Asp-Pro-Val-Val-Val-Cys-Lys-Val-Val-Pro-Cys-Thr-Leu- Ala-Leu .

Amino Acid Sequence↗