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Biomedical subjects

S Kang

Publications and source records attributed to S Kang.

At least 253 records · Page 14Linked to original sources

Steric and electronic relationships among some hallucinogenic compounds.

Stereochemical considerations and total valence electron calculations suggest congruities among the ostensibly dissimilar hallucinogenic compounds, D-lysergic acid diethylamide (LSD), indolcalkylamines, and methoxylated amphetamines. In LSD the aromatic benzene ring A and the N-6 nitrogen are essential for hallucinogenic activity; these sites may react with the receptor. The conformations of amphetamines and indolealkylamines at the receptor are such that the aromatic benzene ring lies like ring A of LSD and the alkylamino nitrogen lies like the N-6 of LSD. Ring A may interact with the receptor by forming a pi-molecular complex, as suggested by the correlation between hallucinogenic activity and energy of the highest occupied molecular orbital (E(H)) of congeneric series. The N-6 nitrogen of LSD and the sterically congruent nitrogen of the other hallucinogenic compounds may react with the receptor by forming a donor acceptor complex of the n-pi(*) or n-sigma(*) type. Other portions of the hallucinogenic molecules confer a favorable E(H): these include the methoxy and hydroxyl groups of the amphetamines (and mescaline), and the indolealkylamines; and the pyrrole ring of LSD and the indolealkylamines.

Amphetamine↗

Derepression of beta-galactosidase synthesis in Escherichia coli K-12 by p-fluorophenylalanine.

p-Fluorophenylalanine (FPA) derepresses beta-galactosidase synthesis at 35 C but not at 25 C in Escherichia coli K-12, strain MC132 (lac I1,2), a strain with a temperature-sensitive lac repressor. In contrast, strain MC130 (lac I(+)) is not derepressed by FPA at 35 C. Temperature-shift experiments with strain MC132 in the presence of FPA and other reagents (isopropyl-1-thio-beta-d-galactoside or chloramphenicol) are consistent with the following mechanism. FPA is incorporated into the genetically altered lac repressor at all temperatures. This further alteration due to incorporation of analogue makes the lac repressor protein inactive at 35 C but active at 25 C. Once an active tertiary structure is formed at 25 C, it is stable at 35 C. However, the inactive tertiary structure of the FPA-containing repressor can assume an active tertiary structure when the temperature is shifted from 35 to 25 C. In the discussion of the results, "inactive tertiary structure" is equated with "monomers" and "active tertiary structure" with oligomers.

Chloramphenicol↗

Induction of capsular polysaccharide synthesis by rho-fluorophenylalanine in Escherichia coli wild type and strains with altered phenylalanyl soluble ribonucleic acid synthetase.

Escherichia coli K-12 strain AB259 can be induced to form capsular polysaccharide (mucoid clones) by dl-p-fluorophenylalanine (FPA; 5 x 10(-6)m on agar plates at 37 C or 8 x 10(-5)m in liquid medium at 30 C). The change was shown to be phenotypic. An increase in enzymes probably involved in capsular polysaccharide synthesis [phosphomannose isomerase (3.3-fold), uridine diphosphate-d-galactose-4-epimerase (2.5-fold), and guanine diphosphate-l-fucose synthetase] was demonstrated as a result of growth in FPA. These increases appear sufficient to account for the increased synthesis of capsular polysaccharide due to growth in FPA. FPA-resistant derivatives of strain AB259 were obtained by selecting mutants on FPA-containing agar or by transducing in an altered phenylalanyl soluble ribonucleic acid synthetase that activates FPA poorly. Mucoid clones were formed by these strains only in the presence of 30 to 1,000 times as much FPA. Among these strains, there was a close correlation between incorporation of FPA-C(14) and induction of capsular polysaccharide synthesis. The results are thus consistent with the following model: FPA is incorporated into the protein product of the R(1) gene (repressor) and alters it sufficiently to allow derepression of several enzymes.

Antimetabolites↗

Derepression of alkaline phosphatase in Escherichia coli by p-fluorophenylalanine.

p-Fluorophenylalanine (FPA) causes a 100-fold increase in alkaline phosphatase in Escherichia coli B, strain PR1 at 30 C in minimal medium that contains excess inorganic phosphate (1.92 x 10(-3)m). Little increase in alkaline phosphatase synthesis occurs under these conditions at 22 C. [This strain is known to have a mutation in a regulator gene (R(2)) that, in the absence of FPA, permits derepression of alkaline phosphatase synthesis at 37 C, but not at 30 C or below.] In contrast, E. coli B3 (the strain from which E. coli B strain PR1 was derived) is not derepressed at 30 C by FPA. (14)C-FPA is incorporated into bacterial proteins. Temperature-shift experiments (30 Cright harpoon over left harpoon22 C) in the presence of FPA are consistent with the following mechanism. FPA is incorporated into the genetically altered R(2) protein at 30 and 22 C. This further alteration due to the incorporation of analogue makes the R(2) protein inactive at 30 C, but active at 22 C.

Alkaline Phosphatase↗

Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide expressed in a wide variety of tumors, and it stimulates angiogenesis and increases vascular permeability. Increased expression of VEGF may be associated with advanced stage and poor prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: Using enzyme-linked immunosorbent assay, the levels of VEGF were determined in serum from 41 patients with untreated NSCLC (Stage: IIB, 3; IIIA, 6; IIIB, 17; IV, 15; HISTOLOGY: squamous cell carcinoma, 18; adenocarcinoma. 14; undetermined, 9). RESULTS: The median VEGF level was 312 pg/ml, ranging from 70 to 1440 pg/ml. Patients were divided into high VEGF (>312 pg/ml) and low VEGF (< or =312 pg/ml) groups using the median value as a cut-off. There were no significant associations between the serum VEGF levels and various clinicopathologic characteristics including age, gender, histologic type, stage and treatment. A significant positive correlation was found between serum VEGF levels and platelet counts (r=0.495; P=0.001). In addition, serum VEGF levels also correlated with leukocyte counts (r=0.478; P=0.002). In seven patients with measurement of follow-up serum VEGF levels at the end of treatment (chemotherapy and/or radiotherapy), the median serum VEGF level significantly decreased after the treatment (416 pg/ml; range, 96-812 pg/ml vs. 185 pg/ml; range, 49-487 pg/ml; P=0.028). However, the median platelet count (317,000/microl; range, 190,000-395,000/microl vs. 246,000/microl; range, 72,000-271,000/microl; P=0.028) and leukocyte count (10,000/microl; range, 8700-17,200/microl vs. 5100/microl; range, 3900-9500/microl; P=0.018) also decreased after the treatment. There was no statistically significant difference in the median survival of the patients between high VEGF group and low VEGF group (8 months vs. 9 months, P=0.647). CONCLUSIONS: Although serum VEGF level was significantly associated with platelet and leukocyte counts in NSCLC patients, it did not correlate with tumor burden and prognosis of the patients.

Adenocarcinoma↗

Ammonia removal using hepatoma cells in mammalian cell cultures.

It was examined whether hepatocyte cell lines can be used for ammonia removal in mammalian cell cultures. It was found that there exists a critical ammonium concentration level for each hepatocyte cell to remove ammonia. Among the cells tested in this work, primary hepatocytes showed the strongest ammonia removal capability if ammonium concentration is higher than the critical level. However, primary hepatocytes lost the liver function gradually and finally died after 2-3 weeks. Because of this limitation, primary hepatocytes were not appropriate to be used for ammonia removal in long-term cultures. Hep G2 cells, which are immortal, also showed a strong ammonia removal activity. The ammonia removal activity of Hep G2 cells depended on the concentration of ammonium in the medium, as in the case of primary hepatocytes. However, urea could not be detected in the course of ammonia removal by Hep G2 cells. Instead of urea, Hep G2 cells secreted glutamine into the culture medium. The capacity for ammonia removal was higher in the absence than in the presence of glutamine. Thus we checked the activity of glutamine synthetase in the Hep G2 cells. The level of glutamine synthetase activity increased with the addition of ammonium chloride. This result accounts for the ammonium concentration dependency of Hep G2 cells in ammonia removal and glutamine synthesis. Furthermore Hep G2 cells could grow well in the absence of glutamine, which was necessarily required in mammalian cell cultures. These results prove that glutamine formation serves as the primary mechanism of detoxifying ammonia in hepatocyte cell lines as expected. In addition, it was demonstrated that ammonium level could be reduced 38% and that erythropoietin production increased 2-fold in the mixed culture of Hep G2 and recombinant CHO cells.

Ammonia↗

The PWL host specificity gene family in the blast fungus Magnaporthe grisea.

The PWL2 gene, isolated from a Magnaporthe grisea rice pathogen, prevents this fungus from infecting a second host grass, weeping lovegrass. We have investigated the distribution of sequences homologous to PWL2 in M. grisea strains isolated from diverse grass species. Multiple PWL2 homologs with varying degrees of sequence homology were identified. The presence of PWL2 homologs does not correlate with an avirulent phenotype on weeping lovegrass in many cases: some strains were fully pathogenic on weeping lovegrass although they carry multiple PWL2 homologs. Three weakly hybridizing PWL2 homologs were cloned and characterized. One of these, the PWL1 gene previously identified by genetic analysis, functioned to prevent infection of weeping lovegrass. Cloned PWL3 and PWL4 genes were nonfunctional, although PWL4 became functional if its expression was driven by either the PWL1 or the PWL2 promoter. The PWL1, PWL2, and PWL3/PWL4 genes map to different genomic locations. The amino acid sequences of the predicted PWL1, PWL3, and PWL4 proteins have 75, 51, and 57% identity, respectively, to the PWL2 protein. Our studies indicate that PWL genes are members of a dynamic, rapidly evolving gene family.

Amino Acid Sequence↗

Polymorphism in the E6 gene of human papillomavirus type 16 in the cervical tissues of Korean women.

The aim of this study was to identify sequence variants in the HPV 16 E6 gene in Korean women and to examine the possible association between these sequence variants and cervical cancer development. We examined the HPV 16 DNA of 215 patients with no cervical disease (NCD) (n = 105) or with cervical neoplasia (n = 110) [cervical intraepithelial neoplasia (CIN), n = 61; invasive cervical carcinoma (ICC), n = 49] using the nested polymerase chain reaction (PCR) and PCR-directed sequencing methods. Fifty-four (NCD, n = 10; CIN, n = 17; ICC, n = 27) of the 215 samples contained HPV 16 E6 DNA, but only two (7.4%) of 27 ICC samples had prototype sequences. The most frequently found variation was D25E (in NCD, n = 8, 80%; in CIN, n = 9, 52.9%; in ICC, n = 23, 85.2%). This is a rare variation in western countries. No significance difference was found between the frequencies of D25E variation in cancerous and non-cancerous lesions. Among the 11 kinds of variants identified, four variants were novel and have been registered with GenBank. This study demonstrates that the D25 variant is the most prevalent E6 genomic variant type in Korean population. However, it was not found to be associated with an increased risk of ICC.

Cervix Uteri↗

Modulation of glucose and growth hormone responses to meals and exercise in type 1 diabetes by cholinergic muscarinic blockade.

Anticholinergic drugs suppress nocturnal and exercise-related growth hormone (GH) secretion in Type 1 diabetes; nocturnal GH suppression is associated with a fall in fasting plasma glucose levels. The aim of this study was to assess the effect of GH suppression on glucose levels following a period of meals and exercise in physiological pattern. Six Type 1 diabetic men recruited from the outpatient clinic were studied in random order at least 1 week apart. After an overnight fast subjects received two-thirds of their usual subcutaneous insulin and either 200 mg oral pirenzepine or placebo at time 0 min. Between 90 and 120 min subjects exercised continuously on an ergometric cycle. Standard meals or snacks were eaten at 30, 150, 270, and 390 min. Venous blood was collected from an indwelling cannula between 0 and 570 min. The mean incremental rise in plasma glucose after breakfast (delta peak/90 min) was 2.6 +/- 0.5 (mean +/- SEM mmol l-1 (pirenzepine) vs 4.5 +/- 0.8 (placebo)), p < 0.05. Following exercise the fall in plasma glucose (delta gluc90-240 min) was 6.4 +/- 1.9 (pirenzepine) vs 2.0 +/- 1.3 (placebo), p < 0.005. The exercise-related peak rise in GH was 12.6 +/- 3.3 (pirenzepine) vs 28.5 +/- 6.0 mU l-1 (placebo), p = 0.08. Excluding one outlying result there was an inverse correlation between the integrated exercise-related increase in GH between 90 and 240 min and the fall in glucose over the corresponding time period (n = 11, r = -0.75, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗