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S K Lim

Publications and source records attributed to S K Lim.

At least 19 recordsLinked to original sources
PubMed1992

Human beta-globin mRNAs that harbor a nonsense codon are degraded in murine erythroid tissues to intermediates lacking regions of exon I or exons I and II that have a cap-like structure at the 5' termini.

Previous studies have demonstrated that nonsense codons within beta zero-thalassemic or in vitro-mutagenized human beta-globin transgenes result in the production of mRNAs that are degraded abnormally rapidly in the cytoplasm of murine erythroid cells. As a consequence, three RNA degradative intermediates are formed that lack sequences from either exon I or exons I and II. We show here that the intermediates, like the full-length mRNA from which they derive and the endogenous murine beta maj-globin mRNA, bind to the anticap monoclonal antibody H-20 in a way that is competed by the cap analogue m7G and eliminated by prior exposure to tobacco acid pyrophosphatase. Furthermore, the intermediates, like the two full-length mRNAs, are resistant to a 5'----3' exonuclease activity isolated from HeLa cell nuclei that degrades uncapped but not capped ribopolymers. Based on these observations, the intermediates appear to possess a structure that is indistinguishable from the cap at the 5' end of mRNA, i.e. a methylated nucleoside that is linked to the RNA by a 5'-5' phosphodiester bond. Detection of the intermediates during murine development was concomitant with detection of full-length thalassemic mRNA. Intermediate production appears to be influenced by RNA structure as indicated by the products that derive from a beta zero-thalassemic beta-globin transgene harboring a structural alteration (a 4 bp deletion) that was larger than any of those previously studied.

Animals↗
PubMed1992

Immunogenetic and nutritional profile in insulin-using youth-onset diabetics in Korea.

There are few reports on the genetic, immunological and nutritional characteristics of insulin-using youth-onset diabetes mellitus, insulin-dependent diabetes mellitus (IDDM) and malnutrition-related diabetes mellitus (MRDM) in Korea. Among 1266 hospitalized Korean diabetics, 29 (2.3%) were IDDM and 84 (6.6%) were MRDM. A diabetes history of first-relatives (28.6%) was more frequently found in the MRDM group than in the IDDM (14.8) and non-insulin-dependent diabetes mellitus (NIDDM) (19.0%) groups. HLA-DR4 was more common among IDDM (54.2%) and MRDM (52.4%) patients than controls (26.3%), and HLA-DR3 was more common among only IDDM patients (29.2%) than controls (10.9%). Conventional islet-cell antibodies were detected in 8 of 15 IDDM patients tested (53.3%) and in 11 of 22 MRDM patients (50.0%). MRDM patients had higher serum basal (1.02 +/- 0.51 ng/ml) and peak (1.44 +/- 0.76 ng/ml) C-peptide concentrations than IDDM patients, but lower concentrations than NIDDM patients. Before the onset of diabetes, the calorie intake of 21 MRDM patients assessed was 63.1% of the daily requirement and the intake of carbohydrate, protein and fat was 71.7%, 55.9% and 39.8%, respectively. In summary, our data suggest that IDDM in Korea is associated with HLA-DR3 or HLA-DR4, indicating a risk for IDDM in Western societies; furthermore, MRDM has a history of undernutrition at the preonset period and is also associated with HLA-DR4. It might be also concluded that MRDM in Korea is another expression of IDDM caused by the shortage of some nutrients for the structural and/or functional maintenance of pancreatic beta-cells.

Adolescent↗
PubMed1992

Allotransplantation of rat islets into the cisterna magna of streptozotocin-induced diabetic rats.

Islets were isolated from the pancreata of Sprague-Dawley rats and transplanted into streptozotocin-induced diabetic outbred Wistar rats. The effect of transplantation of islets into the cisterna magna on the diabetic state of the recipients was compared with that of the conventional transplantation of islets into liver via the portal vein. After successful intraportal (IP) transplantation, rejection took place between days 7 and 15 in all diabetic recipients. All of the eleven rats surviving after stereotaxic implantation of islets into the cisterna magna returned to normoglycemia within 7 days after transplantation. Nine of the recipients with intra-cisterna magna (IM) islet allografts were still normoglycemic at 210 days after transplantation. The glucose disappearance rate of the IM transplant rats was slower than that of the IP transplant rats, and blood glucose returned to the normal basal level within 5 hr following glucose administration. Although the insulin levels were almost undetectable in cerebrospinal fluid before IM transplantation, the insulin levels were markedly increased after IM transplantation and twice as great in CSF than blood. Thus, these findings indicate that the cisterna magna can serve as an immunologically privileged site for implantation of allogeneic pancreatic islets, and islets in CSF can regulate and maintain normal glucose homeostasis via secretion of insulin across the blood-brain barrier.

Animals↗
PubMed1992

Nonsense codons in human beta-globin mRNA result in the production of mRNA degradation products.

Human beta zero-thalassemic beta-globin genes harboring either a frameshift or a nonsense mutation that results in the premature termination of beta-globin mRNA translation have been previously introduced into the germ line of mice (S.-K. Lim, J.J. Mullins, C.-M. Chen, K. Gross, and L.E. Maquat, EMBO J. 8:2613-2619, 1989). Each transgene produces properly processed albeit abnormally unstable mRNA as well as several smaller RNAs in erythroid cells. These smaller RNAs are detected only in the cytoplasm and, relative to mRNA, are longer-lived and are missing sequences from either exon I or exons I and II. In this communication, we show by using genetics and S1 nuclease transcript mapping that the premature termination of beta-globin mRNA translation is mechanistically required for the abnormal RNA metabolism. We also provide evidence that generation of the smaller RNAs is a cytoplasmic process: the 5' ends of intron 1-containing pre-mRNAs were normal, the rates of removal of introns 1 and 2 were normal, and studies inhibiting RNA synthesis with actinomycin D demonstrated a precursor-product relationship between full-length mRNA and the smaller RNAs. In vivo, about 50% of the full-length species that undergo decay are degraded to the smaller RNAs and the rest are degraded to undetectable products. Exposure of erythroid cells that expressed a normal human beta-globin transgene to either cycloheximide or puromycin did not result in the generation of the smaller RNAs. Therefore, a drug-induced reduction in cellular protein synthesis does not reproduce this aspect of cytoplasmic mRNA metabolism. These data suggest that the premature termination of beta-globin mRNA translation in either exon I or exon II results in the cytoplasmic generation of discrete mRNA degradation products that are missing sequences from exon I or exons I and II. Since these degradation products appear to be the same for all nonsense codons tested, there is no correlation between the position of translation termination and the sites of nucleolytic cleavage.

Alleles↗
PubMed1992

The carboxy-terminus of parathyroid hormone is essential for hormone processing and secretion.

The biological function of the carboxy-terminal portion of the PTH molecule is unknown. We hypothesized that the carboxy-terminus of PTH may be essential for hormone processing and secretion. To ascertain the potential role of the carboxy-terminus in transport through the secretory pathway, we constructed a series of carboxy-terminally deleted mutants of human preproPTH. PreproPTH and these truncated peptides were expressed in cell-free extracts and in acutely transfected COS 7 cells. Intact preproPTH(1-84) (115 residues) was processed to proPTH(1-84); the PTH was secreted very efficiently. In contrast, translocation across the membrane of the endoplasmic reticulum and signal sequence cleavage were mildly impaired for PTH(1-52) (83 residues), moderately impaired for PTH(1-40) (71 residues), and dramatically impaired for PTH(1-34) (65 residues). Subsequent cleavage of the prosequence and secretion from intact cells were also dramatically impaired for PTH(1-52) and undetectable for PTH(1-40) and PTH(1-34). We conclude that more than 65 residues are needed to cross the endoplasmic reticulum and that more than 83 residues are needed for efficient prosequence cleavage and secretion. Perhaps similar requirements for full transport through the secretory pathway explains why most secreted peptides are synthesized as long propeptides of at least 80 residues.

Animals↗
PubMed1992

Thyrotropin-secreting pituitary microadenoma.

We present a 45-yr-old male with clinical signs and symptoms of mild hyperthyroidism, high serum levels of T3, T4, and FT4 as well as serum TSH concentration. The elevated alpha-subunit level and alpha-subunit/TSH molar ratio were also observed. These findings indicated the presence of hyperthyroidism due to inappropriate secretion of TSH, whose neoplastic origin was documented by nuclear magnetic resonance scan showing a 0. 6 cm pituitary adenoma. Selective pituitary adenomectomy was completely successful; alpha-subunit, TSH, T3, T 4, and FT4 normalized, and euthyroidism was restored. Light microscopic immunohistochemistry showed that the adenoma was composed of TSH-secreting cells.

Adenoma↗
PubMed1992

Ranitidine and sodium citrate as prophylaxis against acid aspiration syndrome in obstetric patients undergoing caesarean section.

The efficacy of a single oral dose of 0.3M of sodium citrate alone as a prophylaxis against acid aspiration syndrome in obstetric patients undergoing LSCS (elective and emergency) was compared with that of intravenous ranitidine. One group of patients was given 30 ml of 0.3M sodium citrate orally just before the induction of anaesthesia while the other group was given 50mg of ranitidine intravenously together with the 30ml of 0.3M sodium citrate. This was done for both the elective and the emergency groups of patients. There was no significant difference in the mean pH of the gastric aspirate obtained from those given sodium citrate alone and those given sodium citrate and ranitidine in either the elective or the emergency group. However, in the emergency group, those who were given sodium citrate alone tend to have a larger volume of gastric aspiration when compared with those given ranitidine together with the sodium citrate. There were significantly more patients with gastric aspirates of more than 25ml in the emergency group to which sodium citrate alone was given. It would appear that supplementing an intravenous dose of ranitidine with the oral dose of sodium citrate is useful in emergency LSCS as a prophylaxis against acid aspiration syndrome.

Adult↗
PubMed1992

[Effects of fatty acids on hepatic amino acid metabolism in isolated perfused liver in rats].

Large disparity in experimental conditions concerning the use of isolated perfused liver led us to investigate the effects of two free-fatty acids on amino acid metabolism in this model. Oleate uptake was 210 +/- 46 nmol/min.g and octanoate uptake 550 +/- 60 nmol/min.g. Fatty acid utilization led to an increase in ketogenesis, enhanced by octanoate in accordance with its known availability for beta-oxidation. In our experiments neither oleate nor octanoate modified hepatic amino acid exchange and metabolism as assessed by the measurements of amino acids fluxes and glucose and urea production.

Amino Acids↗
PubMed1991

Full-length chicken parathyroid hormone. Biosynthesis in Escherichia coli and analysis of biologic activity.

Chicken parathyroid hormone (cPTH) has been reported to stimulate adrenal steroidogenesis and to have unusual potency on traditional PTH target tissues. To evaluate these properties, chicken PTH-(1-88) has been expressed in Escherichia coli using a plasmid encoding a fusion protein which links together growth hormone, a factor Xa recognition site, and chicken PTH-(1-88). The growth hormone-cPTH fusion protein required the presence of 0.02% sodium dodecyl sulfate to remain in solution and be cleaved by factor Xa. The high performance liquid chromatography-purified recombinant cPTH-(1-88) and chemically synthesized cPTH-(1-34) had similar potency in rat osteosarcoma (ROS 17/2.8) cells, opossum kidney (OK) cells, and dispersed primary chicken kidney cells. The biologic potencies of cPTH-(1-34) and cPTH-(1-88) in radioreceptor binding and cAMP generation in both bone- and kidney-derived cell lines were less than those of human (h)PTH-(1-34). In dispersed chicken kidney cells, cAMP production by cPTH-(1-34) and cPTH-(1-88) was similar to that stimulated by human PTH-(1-34). No stimulation of steroidogenesis could be detected when recombinant chicken PTH-(1-88) was added to dispersed chicken adrenal cells. The biologic activity of recombinant chicken PTH-(1-88) purified from E. coli was comparable with that of chicken PTH-(1-88) expressed by mammalian COS cells. Thus, the full-length chicken PTH did not exhibit enhanced potency, when compared with human PTH in ROS 17/2.8, OK cell lines, and dispersed chicken kidney cells and did not demonstrate the novel steroidogenic action previously reported in adrenal cells. The successful production of chicken PTH-(1-88) will enhance our understanding of the structure-activity relationships for PTH, particularly the sequence-dependent metabolism of the hormone.

Animals↗
PubMed1991

The use of single dose of sodium citrate as a prophylaxis against acid aspiration syndrome in obstetric patients undergoing caesarean section.

The effectiveness of sodium citrate as a prophylaxis against acid aspiration syndrome was studied in 3 groups of obstetric patients. Group I was the control group which consisted of 20 patients in established labour who were not likely to require caesarean section. No antacid had been given to these patients. Group II consisted of 20 patients who underwent elective caesarean section, while Group III consisted of another 20 patients who underwent emergency caesarean section. Group II and III were given 30ml of 0.3M sodium citrate as soon as they arrived in the operation theatre. The gastric content was aspirated after the induction of anaesthesia and at the end of surgery just before extubation. The volume was measured and a sample sent for pH analysis. Sodium citrate was found to increase the gastric pH significantly in both Group II and III patients when compared with Group I patients who underwent emergency caesarean section. We conclude that 30ml of 0.3M sodium citrate is effective in increasing gastric pH though it tends to be associated with an increase in gastric volume.

Cesarean Section↗
PubMed1986

Preliminary observations on the influence of antibiotics on the ecology of Escherichia coli and the enterococci in the faecal flora of healthy young chickens.

Two separate replicated experiments are described. In the first the influence of oxytetracycline on the Escherichia coli flora was assessed, while in the second the effect of tylosin on the enterococci was investigated. In both experiments the administration of the antibiotic was associated with an increase in the average proportion of isolates resistant to the agent although in experiment 1 the agent had no apparent influence on either the total number of E. coli strains, differentiated by biotype and resistance pattern, or the number of 'new' strains per sampling. On the other hand significant differences were noted between the two replicates and also in relation to the age of the birds. In the second experiment fewer enterococcal strains were isolated from the birds dosed with tylosin but since fewer strains on average were isolated from the samples collected prior to dosing it is probable that this difference was due to factors other than the influence of the antibiotic. The enterococci were speciated and the two most commonly isolated were Streptococcus faecalis and S. faecium. The isolation rate of each was expressed as a proportion of the total number of enterococcal isolates per sample and when considered in relation to both dosing and the age of the bird the interaction dosing X age was statistically significant for both species. However, the differences did not appear particularly great and it was possible that the differences were of no practical importance from an ecological point of view.

Animals↗