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Biomedical subjects

S K Lim

Publications and source records attributed to S K Lim.

At least 91 records · Page 5Linked to original sources
PubMed1994

Cytokine response to burn injury: relationship with protein metabolism.

Plasma levels of interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL-6), and markers of protein metabolism were determined in 12 burn patients throughout the healing period (day 2 to 21 post-injury) to determine the pattern of variations in plasma cytokine concentration. To establish the relationship between cytokine production and the nutritional status a wide range of severity standpoints (burn surface area ranging from 9% to 82%) was chosen. Interleukin 6 levels were increased in all patients throughout the study period; maximum concentrations (615 +/- 198 pg/mL) were reached on day 4 and correlated (p < 0.01) with the extent of burn injury. Tumor necrosis factor alpha levels were also elevated; they were significantly higher on day 7 in the patients who developed sepsis than in the other patients (67 +/- 21 pg/mL vs. 20 +/- 7 pg/mL; p < 0.05) but did not correlate with the extent of burn injury. Interleukin 1 beta was rarely detected. Cortisolemia on day 7 was inversely correlated with levels of TNF alpha but not with those of IL-6. Interleukin 6 levels correlated positively with protein turnover (phenylalaninemia) and catabolism (3-methylhistidine/creatinine ratio) and negatively with levels of fibronectin and transthyretin. Our data indicate that the systemic cytokine response to burn injury is mainly represented by IL-6. These data also support the hypothesis that IL-6 is a key mediator of the variations in protein metabolism following burn injury.

Adult↗
PubMed1994

Reduction in size of a thyrotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog).

We present a 55-year-old female with a thyrotropin (TSH)-secreting pituitary adenoma who had been treated with somatostatin analog octreotide acetate (SMS 201-995) for 4 months. Subcutaneous injection of 100 micrograms octreotide acetate twice daily resulted in significant reduction of the TSH, thyroid hormone, and tumor size. During the treatment, there was no evidence of any side effects. We may conclude that octreotide acetate administration is an effective treatment in patients with TSH-secreting pituitary adenoma for suppressing TSH hypersecretion and reducing the size of the tumor.

Adenoma↗
PubMed1994

Reduced growth hormone response to L-dopa and pyridostigmine in obesity.

The purpose of this study was to evaluate growth hormone (GH) secretion and clarify the factors influencing GH secretion in obesity. Nine obese subjects and eight controls were recruited. We compared the GH response to L-dopa with or without pyridostigmine pretreatment in obese and control subjects. Plasma glucose, insulin, insulin-like growth factor I (IGF-I) and free fatty acid (FFA) were also measured. Growth hormone responses and GH area under the response curve (AUC) to L-dopa were significantly lower in obese subjects than those in controls. Pyridostigmine significantly enhanced the GH response to L-dopa in both obese and control subjects. However, enhanced GH responses in obese subjects were attenuated biologically and lower than those in controls with L-dopa only. Plasma levels of insulin insulin and FFA were significantly higher in obese subjects than those in controls. Body mass index had a positive correlation with the levels of insulin and FFA. However, GH AUC had an inverse correlation with insulin and FFA in obese subjects and controls. Stepwise multiple regression analysis showed a highly significant effect of FFA on GH AUC, but no independent influence of other factors on GH AUC. The reduced GH secretion found in this study suggests an increase in somatostatinergic tone and a diminished release of GHRH from the hypothalamus in obesity. However, other factors including hyperinsulinemia and increased plasma FFA may play an important additional role in the secretory dysfunction of GH in obesity.

Adult↗
PubMed1993

Identification of rat epidermal profilaggrin phosphatase as a member of the protein phosphatase 2A family.

The aggregation of cellular intermediate filaments is an important step in the terminal differentiation of keratinocytes. It has been shown that epidermal filaggrin can cause intermediate filaments to aggregate in vitro and may also have the same function in vivo. Filaggrin is derived via dephosphorylation and proteolysis from a highly phosphorylated precursor, profilaggrin, which is found in the granular layer of the epidermis. Using casein kinase II phosphorylated filaggrin as substrate, a profilaggrin phosphatase has been partially purified from rat epidermal homogenate by three chromatographic steps (DE52, hydroxylapatite and S200 gel filtration). Profilaggrin phosphatase activity eluted from the last column has a Km of 0.12 mM and a Vmax of 8 nmol/mg/min with respect to phosphofilaggrin. Results obtained by initial rate analysis showed that the enzymatic activity is not affected by phospho-tyrosyl phosphatase inhibitors and the active fractions preferentially dephosphorylate the alpha subunit of phosphorylase kinase which has been phosphorylated by cAMP-dependent kinase. These results suggest that epidermal profilaggrin phosphatase is not a phospho-tyrosyl phosphatase or a type 1 phospho-seryl/phospho-threonyl phosphatase. Dephosphorylation is not affected by EDTA, calcium or magnesium, but is very sensitive to okadaic acid inhibition (IC50 = 80 pM), suggesting that the enzymatic activity is related to that of the protein phosphatase 2A (PP2A).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Peak bone mass and affecting factors in Korean women.

Maximizing peak bone mass is advocated as a way to prevent osteoporosis. To evaluate the peak bone mass and the affecting factors in Korean women, we analyzed bone stiffness in 116 middle school students, 118 high school students and 115 female college students by using the Achilles densitometer (Lunar Corporation). Peak bone stiffness of Korean women was relatively lower than that of white women (94% of white women) and a rapid rise of bone stiffness was observed in those subjects 3-4 years after menarche. In adolescent females without menstruation, the bone stiffness was lower than that of adolescent girls with menstruation. The factors affecting the peak bone mass was similar to the risk factors of post menopausal osteoporosis: menstruation status, calcium intake and physical activity. The amount of calcium intake in Korean girls at the critical age (3-4 years after menarche) was lower than the RDA (requirement of daily allowance) at this age. To improve any program aimed at maximizing peak bone mass, further intensive study will be required to evaluate some other common factors affecting peak bone mass in Korean.

Adolescent↗
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↗