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Biomedical subjects

K O Lee

Publications and source records attributed to K O Lee.

At least 19 recordsLinked to original sources
PubMed2006

Recurrent episodes of arthritis in a hyperthyroid patient.

Antineutrophil cytoplasmic antibody (ANCA)- associated vasculitis is a potentially life-threatening adverse effect of antithyroid medications. We present a 22-year-old woman with Graves' disease who developed recurrent episodes of arthritis while on treatment with propylthiouracil. A diagnosis of propylthiouracil-induced ANCA-associated vasculitis was established only after exhaustive rheumatological investigations failed to establish a cause for her arthritis. Anti-myeloperoxidase antibody (anti-MPO) titres were grossly elevated at 172.7 RU/mL (0-20). Her arthritis resolved promptly following the withdrawal of propylthiouracil and the anti-MPO titres declined over 16 months to 66.8 RU/mL. While she did not develop the life-threatening renal or respiratory tract complications, there was a delay in establishing the correct diagnosis with its attendant morbidity. This case highlights the need for greater awareness of this relatively rare adverse effect of antithyroid medications so as to allow its early detection, leading to the prompt cessation of the offending medication.

Adult↗
PubMed2005

Parathyroid carcinoma: a case series.

INTRODUCTION: We present 3 patients with parathyroid carcinoma and describe their presentations, clinical profiles, and management. MATERIALS AND METHODS: A case series review of medical records. RESULTS: Two women and 1 man (age range, 32 to 57 years) had parathyroid cancer and primary hyperparathyroidism (PHPT). One patient presented with osteitis fibrosa, 1 with renal stone and a neck mass, and 1 with recurrence of PHPT after excision of supposedly benign parathyroid adenoma 4 years ago. All had severe hypercalcaemia and elevated parathyroid hormone levels that ranged from 4 to 43 times above the normal range. Exploration of the neck clearly identified 1 parathyroid tumour with local invasion; 2 other specimens showed capsular and vascular invasion on frozen section and final histology. All 3 patients underwent parathyroidectomy and ipsilateral hemithyroidectomy. Parathyroid size ranged from 1.3 to 4 cm and no lymph node metastasis was identified. No patient had tumour recurrence after a follow-up period of 1 year. CONCLUSION: Parathyroid carcinoma is a rare endocrine malignancy. Suspicious features include marked hypercalcaemia, neck mass, and local recurrence. Parathyroidectomy with ipsilateral hemithyroidectomy and nodal clearance gives the best chance of reducing local tumour recurrence.

Adult↗
PubMed2004

Does growth hormone prevent aging in the healthy elderly with low serum insulin-like growth factor-I ?

Aging is associated with a gradual decline in the function of a number of endocrine glands. While there are phenotypic similarities seen in the changes of aging with some endocrine hormone deficiency states, the relationship between the decline in growth hormone (GH) secretion, and the decrease in serum insulin-like growth factor-I (IGF-I), with these body composition changes is far from clear. The decline in serum IGF-I, unlike that of thyroxine and estradiol, is not accompanied by an increase in pituitary GH secretion. The recent enthusiastic recommendation for GH 'replacement' in the aging population with low serum IGF-I remains highly controversial. The evidence is still unclear on any significant beneficial effect of such replacement in healthy fit elderly men and women. There is some early evidence of beneficial effects of such replacement in the frail elderly. There are no studies that have investigated the effect of GH on longevity in humans, but results from animal studies on caloric restriction and longevity do not suggest that GH administration will increase life span. There is still insufficient evidence that treatment with exogenous GH in the healthy elderly that attains serum IGF-I levels similar to that of young adults is beneficial or safe.

Aging↗
PubMed2004

Anaplastic thyroid carcinoma with destructive thyrotoxicosis in a patient with preexisting multinodular goiter.

Presentation of anaplastic thyroid carcinoma with thyrotoxicosis is extremely rare and its occurrence in a patient with Wegener's granulomatosis has not been reported previously. We describe an elderly lady with Wegener's granulomatosis who developed a rapidly growing anaplastic thyroid carcinoma in a preexisting multinodular goiter and discuss the mechanism of thyrotoxicosis in this patient.

Aged↗
PubMed2001

Autocrine human growth hormone (hGH) regulation of human mammary carcinoma cell gene expression. Identification of CHOP as a mediator of hGH-stimulated human mammary carcinoma cell survival.

By use of cDNA array technology we have screened 588 genes to determine the effect of autocrine production of human growth hormone (hGH) on gene expression in human mammary carcinoma cells. We have used a previously described cellular model to study autocrine hGH function in which the hGH gene or a translation-deficient hGH gene was stably transfected into MCF-7 cells. Fifty two of the screened genes were regulated, either positively () or negatively (), by autocrine production of hGH. We have now characterized the role of one of the up-regulated genes, chop (gadd153), in the effect of autocrine production of hGH on mammary carcinoma cell number. The effect of autocrine production of hGH on the level of CHOP mRNA was exerted at the transcriptional level as autocrine hGH increased chloramphenicol acetyltransferase production from a reporter plasmid containing a 1-kilobase pair fragment of the chop promoter. The autocrine hGH-stimulated increase in CHOP mRNA also resulted in an increase in CHOP protein. As a consequence, autocrine hGH stimulation of CHOP-mediated transcriptional activation was increased. Stable transfection of human CHOP cDNA into mammary carcinoma cells demonstrated that CHOP functioned not as a mediator of hGH-stimulated mitogenesis but rather enhanced the protection from apoptosis afforded by hGH in a p38 MAPK-dependent manner. Thus transcriptional up-regulation of chop is one mechanism by which hGH regulates mammary carcinoma cell number.

Breast Neoplasms↗
PubMed2001

The effects of autocrine human growth hormone (hGH) on human mammary carcinoma cell behavior are mediated via the hGH receptor.

The human GH (hGH) antagonist B2036 combines a single amino acid substitution impairing receptor binding site 2 (G120K) with eight additional amino acid substitutions that improve binding site 1 affinity. B2036 does not bind, activate, or antagonize the human PRL receptor and therefore is suitable to determine cellular effects mediated specifically through the hGH receptor. We have used this hGH receptor specific antagonist in MCF-7 cells stably transfected with either the hGH gene (MCF-hGH) or a translation deficient hGH gene (MCF-MUT) to determine whether the effects of autocrine hGH on mammary carcinoma cell behavior are mediated via the hGH receptor. Enhanced JAK2 tyrosine phosphorylation observed in MCF-hGH cells compared with MCF-MUT cells is abrogated by B2036 as is the autocrine hGH stimulated increase in total cell number and DNA synthesis. Interestingly, autocrine hGH functions as a potent inhibitor of apoptosis induced by serum withdrawal compared with exogenously added hGH, and the protection against apoptosis afforded by autocrine hGH is abrogated by B2036. B2036 also inhibited autocrine hGH stimulated transcriptional activation mediated by either STAT5, CHOP (p38 MAP kinase specific) or Elk-1 (p44/42 MAP kinase specific). Finally, B2036 inhibited the autocrine hGH-dependent enhancement of the rate of mammary carcinoma cell spreading on a collagen matrix. Thus, the effects of autocrine hGH on human mammary carcinoma cell behavior are mediated via the hGH receptor.

Apoptosis↗
PubMed2001

IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH.

OBJECTIVE: Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH. DESIGN AND METHODS: Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot. RESULTS: Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment. CONCLUSIONS: There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.

Adolescent↗
PubMed2000

Rice 1Cys-peroxiredoxin over-expressed in transgenic tobacco does not maintain dormancy but enhances antioxidant activity.

Possible functions that have been proposed for the plant 1Cys-peroxiredoxin, include activity as a dormancy regulator and as an antioxidant. The transcript level of rice 1Cys-peroxiredoxin (R1C-Prx) rapidly decreased after imbibition of rice seeds, but the protein was detected for 15 days after imbibition. To investigate the function of this protein, we generated transgenic tobacco plants constitutively expressing the R1C-Prx gene. The transgenic R1C-Prx plants showed a germination frequency similar to control plants. However, the transgenic lines exhibited higher resistance against oxidative stress, suggesting that antioxidant activity may be its primary function.

Animals↗
PubMed2000

Autocrine human growth hormone enhancement of human mammary carcinoma cell spreading is Jak2 dependent.

We investigated the role of autocrine production of human (h) GH in the attachment and spreading of mammary carcinoma cells in vitro. We used a previously described model system for the study of the autocrine/paracrine role of GH in which the hGH gene (MCF-hGH) or a translation-deficient hGH gene (MCF-MUT) was stably transfected into MCF-7 cells. No differences in attachment to a collagen matrix between MCF-hGH and MCF-MUT cells were observed in either serum-free medium (SFM) or medium containing exogenous hGH, 5% serum, or 10% serum. In contrast, MCF-hGH cells spread more rapidly on a collagen matrix than did MCF-MUT cells. Exogenous hGH and 10% serum interacted with autocrine production of hGH in an additive manner to increase cell spreading. MCF-hGH cells formed filipodia and stress fibers earlier than MCF-MUT cells during the process of cell spreading and possessed marked differences in morphology after spreading. MCF-MUT cells displayed uniform and symmetrical formation of stress fibers, whereas MCF-hGH cells displayed irregular and elongated stress fiber formation. The level of cytoplasmic phosphotyrosine was increased in MCF-hGH compared with MCF-MUT cells during spreading and displayed colocalization with Janus kinase 2 (JAK2). Basal JAK2 tyrosine phosphorylation was increased, and it increased further on spreading in MCF-hGH cells compared with MCF-MUT cells. Transient transfection of JAK2 complementary DNA resulted in interaction with autocrine hGH to increase the rate of cell spreading in MCF-hGH cells compared with MCF-MUT cells. Treatment with a selective JAK2 tyrosine kinase inhibitor (AG 490) reduced the rate of MCF-hGH cell spreading to the rate of MCF-MUT cell spreading. Thus, we conclude that autocrine production of hGH enhances the rate of mammary carcinoma cell spreading in a JAK2-dependent manner.

Actins↗
PubMed1999

Differential binding properties of oripavines at cloned mu- and delta-opioid receptors.

This study examines the possibility that oripavine opioid receptor agonists bind equally to both high and low affinity states of the mu-opioid receptor. Studies were performed in C6 cells expressing mu- or delta-opioid receptors; high and low agonist affinity states of the receptors were defined by the absence and presence, respectively of Na+ ions and the GTP analog Gpp(NH)p. At the mu-opioid receptor dihydroetorphine and etorphine were full agonists, buprenorphine had moderate efficacy while diprenorphine was an antagonist. At the delta-opioid receptor, dihydroetorphine, etorphine, and diprenorphine had moderate efficacy while buprenorphine was an antagonist. The binding affinities of the oripavines at the mu-opioid receptor decreased only one to 2-fold in the presence of NaCl and Gpp(NH)p. In contrast, decreases in oripavine affinity at the delta-opioid receptor correlated with delta-opioid receptor efficacy. The ability of oripavine agonists to bind with high affinity to the low agonist affinity state of the nu-opioid receptor may explain the high potencies of these compounds in vivo.

Analgesics, Opioid↗
PubMed1999

Autocrine stimulation of human mammary carcinoma cell proliferation by human growth hormone.

Here we have investigated the role of autocrine production of human growth hormone (hGH) in the proliferation of mammary carcinoma cells (MCF-7) in vitro. MCF-7 cells were stably transfected with an expression plasmid encoding the hGH gene, and these cells (designated MCF-hGH) synthesized hGH in the cell and secreted hGH to the medium. For control purposes, a MCF cell line was generated (MCF-MUT) in which the start codon of the hGH gene was disabled, and these cells transcribed the hGH gene without translation to hGH protein. The MCF-hGH cell number increased at a rate significantly greater than that of MCF-MUT under serum-free conditions. Autocrine hGH also synergized with 10% serum and insulin-like growth factor-1 but not 17-beta-estradiol to increase cell number. The increased proliferation of MCF-hGH cells in both serum-free and serum-containing media could be completely abrogated by the use of the nonreceptor dimerizing hGH antagonist, hGH-G120R. Increased mitogenesis as a consequence of autocrine production of hGH was prevented by inhibition of either the p38 MAPK or p42/44 MAPK pathways. MCF-hGH cells also possessed a higher level of STAT5 (but not STATs 1 and 3) mediated transcriptional activation in both serum-free and serum-containing conditions than MCF-MUT cells. Thus we conclude that hGH can act in an autocrine/paracrine manner in human mammary carcinoma cells to promote cell proliferation and transcriptional activation.

Adenocarcinoma↗
PubMed1999

Cloning and expression of a new isotype of the peroxiredoxin gene of Chinese cabbage and its comparison to 2Cys-peroxiredoxin isolated from the same plant.

A cDNA encoding a newly identified isotype of peroxiredoxin (Prx) was isolated from a Chinese cabbage flower bud cDNA library and designated CPrxII. Database searches using the predicted CPrxII amino acid sequence revealed no substantial homology to other proteins with the exception of the yeast type II Prx with which CPrxII shares 27.8% sequence identity. Recombinant CPrxII expressed in Escherichia coli was able to protect glutamine synthetase from inactivation in a metal-catalyzed oxidation system and to reduce H2O2 with electrons provided by thioredoxin. This specific antioxidant activity of CPrxII was about 6-fold higher than that of 2Cys-Prx of the same plant. In contrast to 2Cys-Prx, which is predominantly expressed in leaf tissue of cabbage seedlings, CPrxII is highly expressed in root tissue as revealed by Northern and Western blot analyses. The CPrxII gene exists as a small multigene family in the cabbage genome.

Amino Acid Sequence↗
PubMed1999

Determination of very-long-chain fatty acids in serum by gas chromatography-nitrogen-phosphorus detection following cyanomethylation.

A sensitive method for very-long-chain fatty acid analysis was developed by gas chromatography-nitrogen-phosphorus detection by using cyanomethyl derivatization. Bromoacetonitrile as alkylating reagent was used to improve nitrogen phosphorus detection detectability of compounds containing non-nitrogen. The carboxyl group of very-long-chain fatty acid was alkylated to cyanomethyl esters. Reaction conditions were 40 min at 60 degrees C under potassium carbonate base. Heptacosanoic acid was used as an internal standard and hexane was used as a solvent of extraction. The extraction yield was 82.8% or more, relative standard deviation of the precision test was 8.3% or more and the result of linearity test showed a good correlation coefficient of r2=0.999 in the range of 0.1-50 microg/ml. The quantification limits were 10 ng/ml when 0.5 ml of serum was used. The present method proved simple, rapid, inexpensive and resistant to contaminants. When it was applied to serum samples taken from patients with X-linked adrenoleukodystrophy which is a hereditary X-linked disorder characterized by progressive demyelination and adrenal insufficiency during childhood, relative increase of the concentration of hexacosanoic acid and the concentration ratios of hexacosanoic, lignoceric to behenic acid was observed in comparison with control samples.

Adrenoleukodystrophy↗
PubMed1999

Characterization of two fungal-elicitor-induced rice cDNAs encoding functional homologues of the rab-specific GDP-dissociation inhibitor.

By using the mRNA differential display approach to isolate defense signaling genes active at the early stage of fungal infection two cDNA fragments with high sequence homology to rab-specific GDP-dissociation inhibitors (GDIs) were identified in rice (Oryza sativa L.) suspension cells. Using polymerase-chain-reaction products as probes, two full-length cDNA clones were isolated from a cDNA library of fungal-elicitor-treated rice, and designated as OsGDI1 and OsGDI2. The deduced amino acid sequences of the isolated cDNAs exhibited substantial homology to Arabidopsis rab-GDIs. Northern analysis revealed that transcripts detected with the 3'-gene-specific DNA probes accumulated to high levels within 30 min after treatment with a fungal elicitor derived from Magnaporthe grisea. The functionality of the OsGDIs was demonstrated by their ability to rescue the Sec19 mutant of Saccharomyces cerevisiae which is defective in vesicle transport. The proteins, expressed in Escherchia coli, cross-reacted with a polyclonal antibody prepared against bovine rab-GDI. Like bovine rab-GDI, the OsGDI proteins efficiently dissociated rab3A from bovine synaptic membranes. Using the two-hybrid system, it was shown that the OsGDIs specifically interact with the small GTP-binding proteins belonging to the rab subfamily. The specific interaction was also demonstrated in vitro by glutathione S-transferase resin pull-down assay.

Animals↗
PubMed1999

Molecular cloning, expression, and functional characterization of a 2Cys-peroxiredoxin in Chinese cabbage.

A cDNA (C2C-Prx) corresponding to a 2Cys-peroxiredoxin (2Cys-Prx) was isolated from a leaf cDNA library of Chinese cabbage. The predicted amino acid sequence of C2C-Prx has 2 conserved cysteines and several peptide domains present in most of the 2Cys-Prx subfamily members. It shows the highest sequence homology to the 2Cys-Prx enzymes of spinach (88%) and Arabidopsis (86%). Southern analysis using the cDNA insert of C2C-Prx revealed that it consists of a small multigene family in Chinese cabbage genome. RNA blot analysis showed that the gene was predominantly expressed in the leaf tissue of Chinese cabbage seedlings, but the mRNA was generally expressed in most tissues of mature plant, except roots. The expression of C2C-Prx was slightly induced by treatment with H2O2 (100 microM) or Fe3+/O2/DTT oxidation system, but not by ABA (50 microM) or GA3 (10 microM). The C2C-Prx is encoded as a preprotein of 273 amino acids containing a putative chloroplast-targeting signal of 65 amino acids at its N-terminus. The N-terminally truncated recombinant protein (deltaC2C-Prx) migrates as a dimer in a non-reducing SDS-polyacrylamide gel and as a monomer in a reducing condition. The deltaC2C-Prx shows no immuno cross-reactivity to antiserum of the yeast thiol-specific antioxidant protein, and vice versa. The deltaC2C-Prx prevents the inactivation of glutamine synthetase and the DNA cleavage in the metal-catalyzed oxidation system. In the yeast thioredoxin system containing thioredoxin reductase, thioredoxin, and NADPH, the deltaC2C-Prx exhibits peroxidase activity on H2O2.

Amino Acid Sequence↗
PubMed1999

Comparison of monthly intramuscular injections of Sandostatin LAR with multiple subcutaneous injections of octreotide in the treatment of acromegaly; effects on growth hormone and other markers of growth hormone secretion.

OBJECTIVE: To compare the effects of monthly intra-muscular injections of a long acting preparation of octreotide, Sandostatin LAR, with multiple daily subcutaneous injections of octreotide and to study the interrelationships between mean 24 h growth hormone profile, serum total and free IGF-1 levels, 24 h urinary growth hormone levels and serum IGFBP-3. DESIGN: Patients were assessed by 24 h GH profile off octreotide or any other GH modifying drug therapy; on subcutaneous octreotide (200-600 micrograms daily in divided doses for six weeks); and 28 days after the second of two injections of Sandostatin LAR (20 mg by intra-muscular injection) administered 28 days apart. Serum total and free IGF-1, serum IGFBP-3 and 24 h urinary GH were also measured on each occasion. RESULTS: Sandostatin LAR was well tolerated. None of the patients reported any adverse effect and all completed the study uneventfully. Mean GH off treatment was 10.1 +/- 3.0 micrograms/l falling equally significantly (P < 0.05) during therapy with subcutaneous octreotide to 3.0 +/- 0.7 micrograms/l and Sandostatin LAR to 2.8 +/- 0.7 micrograms/l. Fasting 0900 h GH was significantly reduced (P < 0.05) on Sandostatin LAR (3.0 +/- 0.7 micrograms/l) compared with subcutaneous octreotide (5.1 +/- 1.2 micrograms/l). Mean total IGF-1 off treatment was 658.6 +/- 56.1 micrograms/l and was reduced to a comparable extent with subcutaneous octreotide and Sandostatin LAR (466.0 +/- 59.7 and 448.6 +/- 59.5 micrograms/l respectively; both P < 0.05). Free IGF-1 off treatment was 3.1 +/- 0.6 micrograms/l and was reduced equally by subcutaneous octreotide and Sandostatin LAR (1.2 +/- 0.2 and 1.2 +/- 0.2 micrograms/l; both P < 0.05). IGFBP-3 was reduced to a greater extent during Sandostatin LAR than during subcutaneous octreotide (4518.2 +/- 247.3 vs 5132.8 +/- 280.7 micrograms/l; P < 0.05). Twenty-four hour urinary GH excretion was reduced to a comparable extent with both therapies. Highly significant positive correlations were found between mean 24 h GH levels and free IGF-1 (r = 0.66, P < 0.0001) and 24 h urinary GH excretion (r = 0.94, P < 0.0001). The relationships between mean 24 h GH levels and total IGF-1 and IGFBP-3 although significant showed less powerful correlations. CONCLUSIONS: These results suggest that Sandostatin LAR is well tolerated and as effective as subcutaneous octreotide. In addition, urinary growth hormone and serum free IGF-1 may prove valuable for outpatient follow-up of acromegalic patients, as both correlate well with mean 24 h serum growth hormone levels.

Acromegaly↗