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Biomedical subjects

K O Lee

Publications and source records attributed to K O Lee.

At least 37 records · Page 2Linked to original sources
PubMed1999

Insulin-like growth factor binding proteins (IGFBPs) and IGFBP-related protein 1-levels in cerebrospinal fluid of children with acute lymphoblastic leukemia.

Abnormalities in insulin-like growth factor binding proteins (IGFBPs) have been reported in the cerebrospinal fluid (CSF) of children with acute leukemia. In the present study, we have further characterized the IGFBPs in whole CSF prospectively in 11 children with acute B-lineage lymphoblastic leukemia (ALL) undergoing chemotherapy. Western ligand blots Western immunoblots using a new anti-IGFBP-6 and a new IGFBP-rP1 (related protein-1 antibody and immunoassays (Diagnostic Systems Laboratories, Inc., Webster, TX) were used to characterize and measure IGFBP-6, IGFBP-2, IGFBP-3, and IGFBP-rP1 in children with ALL at diagnosis, and with treatment. Comparisons at baseline were made with 11 children with meningitis and 11 children with febrile convulsions (controls). The mean (+/- SE) CSF IGFBP-6 in ALL patients, 56 (+/- 7) ng/mL, was significantly lower than in meningitis, 97 (+/- 17) ng/mL; and in controls, 123 (+/- 24) ng/mL (P < 0.05, t test). In contrast, CSF IGFBP-3 was elevated in ALL patients, 29 (+/- 9) ng/mL; compared with meningitis, 11 (+/- 1) ng/mL; and controls, 10 (+/- 1) ng/mL (P < 0.05, t test); and IGFBP-2 did not differ among the three groups (47-59 ng/mL, P > 0.05). CSF IGFBP-6 remained very low in the patients with ALL, at 4 and 36 weeks of treatment; whereas IGFBP-3 decreased to control levels, and IGFBP-2 did not change significantly. At baseline, Western ligand blots and Western immunoblots identified a 25- to 28-kDa broad band as IGFBP-6 and a 30-kDa band as IGFBP-2 and showed that there was almost no intact IGFBP-3 in CSF. IGFBP-rP1 was also present in the CSF and was elevated in patients with ALL, compared with the 2 control groups. In conclusion, at diagnosis, IGFBP-rP1 and fragments of IGFBP-3 are elevated, and IGFBP-6 is significantly decreased, in the CSF of ALL children; and IGFBP-6 remained low, with treatment, up to 36 weeks. The role of the IGFBPs and IGFBP-rPs in central nervous system acute leukemia remain to be further elucidated.

Carrier Proteins↗
PubMed1999

Serum IGF-binding protein-6 and prostate specific antigen in breast cancer.

OBJECTIVE: Recent studies have demonstrated the presence of the IGF-binding proteins (IGFBPs) and prostate specific antigen (PSA), an IGFBP protease. in human breast tissue. We sought to investigate the differences in serum IGFs, IGFBP-1, -3 and -6, and PSA between patients with surgically proven breast cancer and patients with benign breast disease. DESIGN AND METHODS: Concentrations of IGFs, IGFBP-1, -3 and -6, and PSA were determined in the sera from 57 patients with breast cancer (CA), and 46 women with benign breast disease (BBD) using immunoassays for IGFs and IGFBPs and an ultrasensitive ELISA for PSA. RESULTS: The mean (+/- S.E.M.) serum IGFBP-6 level in the CA group, 127 (16) ng/ml, was statistically significantly lower than in the BBD group, 157 (10) ng/ml (P = 0.016). Patients with CA had an elevated geometric mean serum PSA level of 0.018 (range: 0.0015-0.107) ng/ml, compared with 0.007 (range: 0.0015-0.019) ng/ml in women with BBD (P = 0.025). Mean serum IGFBP-1 concentrations were significantly lower in the CA group, 16 (2) ng/ml, versus 37 (4) ng/ml in the BBD group (P = 0.001). Mean serum IGFBP-3 concentrations were also lower in the CA group versus the BBD group, at 1981 (65) ng/ml, versus 2603 (140) ng/ml (P = 0.002) respectively. In the CA group, statistically significant correlations between PSA and IGFBP-6 (r = 0.413; P = 0.001), and between PSA and IGFBP-1 (r = -0.329; P = 0.021) were seen. Differences in IGF-I and -II between the two groups were not statistically significant. CONCLUSION: Lower serum concentrations of IGFBP-6, -3 and -1, but higher PSA concentrations were seen in the breast cancer group, and collectively these would suggest that there is an increase in bioavailable IGF-I in breast cancer.

Breast Neoplasms↗
PubMed1998

Tamoxifen alters levels of serum insulin-like growth factors and binding proteins in postmenopausal breast cancer patients: a prospective paired cohort study.

BACKGROUND: Recent data suggest that tamoxifen may act by altering serum levels of insulin-like growth factors (IGFs) and their binding proteins (BPs). This prospective paired cohort study evaluated the influence of tamoxifen on serum levels of IGFs and BPs in postmenopausal patients with breast cancer. METHODS: Blood was collected from 32 postmenopausal patients with breast cancer before and during tamoxifen therapy for at least 6 months. All patients had undergone primary surgery. Serum concentrations of IGF-I, IGF-II, BP-1, and BP-3 were determined by immunoradiometric assays, and Western ligand blots provided a semiquantitative measurement of BP-2, BP-3, and BP-4. Statistical analysis was performed by paired Student's t-test. RESULTS: Mean serum IGF-1 level was significantly lower after tamoxifen treatment (pretreatment: 116.2 ng/mL+/-13.6 [SEM] vs. posttreatment: 77.5 ng/mL+/-7.8; P=.003). In contrast, mean IGF-II levels increased from 651.5+/-62.2 ng/mL to 812.5+/-35.1 ng/mL during treatment (P=.006). Posttreatment levels of BP-1 (92.9 ng/mL+/-7.5) were significantly higher compared to the pretreatment values (28.1 ng/mL+/-4.7; P <.001). Serum concentration of BP-3 also was elevated (pretreatment: 2228.1 ng/mL+/-145.2 vs. posttreatment: 3539.1 ng/mL+/-172.3; P <.001). Densitometric measurements showed a similar significant increase in BP-3 (P <.001) as well as BP-4 (P=.017) after hormonal therapy. Levels of BP-2 were not influenced by tamoxifen treatment. CONCLUSIONS: These significant alterations in serum concentrations of IGFs and BPs with tamoxifen therapy suggest that the IGF system is a potential mechanism by which tamoxifen exerts its growth inhibitory effect on breast carcinomas.

Aged↗
PubMed1998

Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) has mitogenic properties for breast cancer cell lines and has been proposed to be an important factor in breast carcinogenesis. We hypothesized that differences in IGF-1 or its binding proteins might increase susceptibility to breast cancer. This case-control study was designed to investigate whether patients with breast cancer have altered levels of either IGF-1 or its intermediary modulatory proteins, the IGF binding proteins (BP). METHODS: Serum was collected from 90 patients (63 with breast cancer and 27 with benign breast disease) after an overnight fast and before surgery. IGF-1, BP1, and BP3 levels were determined by immunoradiometric assays. In a subset of 66 patients, Western ligand blots were also performed for a semiquantitative measurement of functioning BP levels. A forward stepwise logistic regression model to adjust for other confounding variables (age, menopausal status, parity, age at menarche, use of oral contraceptives, history of breast biopsy, family history of breast cancer, hormone replacement therapy, and body-mass index) was used in the multivariate analysis. RESULTS: Serum IGF-1 levels were similar in cases and controls. However, levels of BP3 (p < 0.001), BP4 (p < 0.01), and BP1 (p < 0.05) were significantly associated with risk of breast cancer. The level of BP3 was the most significant factor predictive of breast cancer. The odds ratio for breast cancer in women with BP3 levels >2066 ng/ml was 0.18 (95% CI, 0.05-0.55). Correspondingly, women with BP1 levels higher than 39 ng/ml had an odds ratio of 0.21 (95% CI, 0.07-0.68) for breast cancer. When considering only cancer patients (n = 63), decreasing levels of BP4 (p < 0.01) and increasing levels of BP1 (p < 0.02) were significantly associated with progesterone receptor positivity (PR+) in the tumor. The odds ratio of PR+ in patients with BP1 levels higher than 34 ng/ml was 7.49 (95% CI, 1.5-37.4). Better grade of tumor (well and moderately differentiated) was observed in patients with higher levels of BP3 (p < 0.03). CONCLUSIONS: Distinct differences in BP profiles exist among patients with breast cancer and also among those with high-grade, hormonal receptor-negative tumors. These findings suggest that the bioavailability of IGF-1 as mediated by its binding proteins may participate in both breast carcinogenesis and selection of more aggressive breast carcinomas.

Age Factors↗
PubMed1998

Effect of insulin-like growth factors (IGFs) and IGF-binding proteins on in vitro sperm motility.

OBJECTIVE: Previous studies have shown that exogenous growth hormone (GH) produces increases in sperm motility when given to subfertile men. Previous studies have also demonstrated the presence of IGFs and IGFBPs in seminal plasma. We have therefore investigated the effects of insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein 2 (IGFBP-2) and intact IGFBP-3 on in vitro sperm motility. DESIGN AND METHODS: Using computer-aided sperm analysis, we investigated the effects of IGFs and IGFBPs on the in vitro sperm motility parameters: curvilinear velocity (CV), progressive velocity (PV), linearity (Ln), straightness (St), amplitude of lateral head movement (ALH), and beat frequency (BF). Washed motile sperm selected by the 'swim-up' method, from normozoospermic samples, were incubated at 37 degrees C in 5% CO2 in air with IGF-I, IGF-II, IGFBP-2, IGFBP-3, or control Earle's media, and were examined at time 0 and after 60 min incubation. Changes in motility parameters after 60 min incubation were compared with controls by analysis of variance (ANOVA). RESULTS: Compared to controls, statistically significant changes occurred at time 60 min after incubation: IGF-I decreased CV and ALH significantly (P < 0.05), but IGFBP-3 increased Ln, St, BF, and decreased ALH significantly (P < 0.05). In contrast, IGF-II, IGFBP-2, and a combination of IGF-I/IGFBP-3, had no significant effects. CONCLUSIONS: IGF-I and IGFBP-3 have differing and opposing effects on in vitro sperm motility parameters and thus may have a role in modulating in vivo sperm motility.

Cell Separation↗
PubMed1998

Distribution of genotypes in the 5' untranslated region of hepatitis C virus in Korea.

Hepatitis C virus (HCV) is an important human pathogen that can cause acute and chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Recently, partial and entire sequence data from HCV isolates have been reported, suggesting various genotypes of HCV. The genotype may be correlated with the progression of hepatitis and maybe a prognostic marker of treatment. Thus, the availability of an assay for typing HCV RNA is important. This study developed a convenient method for genotyping HCV into six groups by PCR-RFLP with four restriction endonucleases (BstUI, HaeIII, NciI, RsaI) in the 5' untranslated region (UTR) of HCV. The HCV genotypes from 169 patients with HCV infections in Korea were analysed. Two genotypes, type 1b and type 2a, accounted for 47.3% and 42.6% of HCV infections, respectively.

Base Sequence↗
PubMed1998

Protective action of capsaicin and chilli on haemorrhagic shock-induced gastric mucosal injury in the rat.

Chilli and its pungent ingredient, capsaicin, have been shown to protect against experimental gastric mucosal injury induced by various necrotizing agents such as ethanol and aspirin and stress. We investigated the effect of capsaicin and long-term ingestion of chilli on haemorrhagic shock-induced gastric mucosal injury in the rat. Anaesthetized male Sprague-Dawley rats were subjected to haemorrhagic shock by withdrawing blood to reduce the mean arterial blood pressure to 30-40 mmHg with subsequent reinfusion of shed blood. This resulted in gastric mucosal injury with readily identifiable haemorrhagic lesions. Capsaicin (5 mg) administered prior to, but not after, haemorrhagic shock, significantly reduced the gastric mucosal injury in intact animals. Sensory ablation with capsaicin pretreatment (125 mg/kg bodyweight) abolished the gastroprotective effect afforded by capsaicin. Similarly, 4 week intake of chilli powder (360 mg daily) reduced the gastric mucosal injury in intact, but not in capsaicin-desensitized rats. Capsaicin and long-term chilli intake protected against haemorrhagic shock-induced gastric mucosal injury and the protection may be mediated by capsaicin-sensitive afferent neurons. Our studies are of potential significance in the context of stress ulcer disease in the human.

Animals↗
PubMed1998

Does a positive oestrogen feedback on the hypothalamic-pituitary axis exist concurrently with a defective testosterone feedback in Klinefelter's syndrome?

The oestrogen provocation and GnRH challenge tests were carried out in 5 subjects with Klinefelter's syndrome who had no history of previous hormonal therapy. The oestrogen provocation test consisted of an intramuscular injection of 10 mg of oestradiol valerate and blood samples were collected daily from day 0 to day 5. In 2 subjects, three GnRH challenge tests were carried out before (day 0) and on days 2 and 4 after the intramuscular injection of oestradiol valerate. During each GnRH challenge test, 7 blood samples were collected at 30-min intervals, 30 min and immediately before and for 150 min after the bolus dose of GnRH. Plasma concentrations of FSH, LH, testosterone and oestradiol were measured by established radioimmunoassays. Plasma levels of oestradiol rose significantly a day following the intramuscular injection of 10 mg of oestradiol valerate, reaching a peak on day 2 and then falling significantly to lower levels by days 4 and 5, although these levels were still significantly higher than the corresponding baseline levels. In the presence of high levels of oestradiol, the high basal levels of FSH were significantly suppressed, and remained suppressed throughout the 5 days of the study. LH, on the other hand, had a biphasic response; an initial significant suppression by day 1 persisting to day 3, but by days 4 and 5 a rebound in basal LH levels was noted. However, the levels on day 5 were not significantly higher than baseline levels. The pituitary responsiveness as far as the LH and FSH secretions were concerned reflected the baseline levels. The results of the present study refuted the claim that a positive oestrogen feedback exists in men including Klinefelter's syndrome as a result of the removal of or reduced testosterone. In addition, the attenuated testosterone feedback in Klinefelter's syndrome is responsible for the greatly amplified pituitary responsiveness to the trophic action of GnRH and this, in part, may be responsible for the elevated levels of FSH and LH seen in such patients.

Estradiol↗
PubMed1998

Analgesic, respiratory and heart rate effects of cannabinoid and opioid agonists in rhesus monkeys: antagonist effects of SR 141716A.

This study characterized the antinociceptive, respiratory and heart rate effects of the cannabinoid receptor agonists Delta-9-tetrahydrocannabinol (Delta-9-THC) and WIN 55212 ((R)-(+)-2, 3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol-[1,2,3-de]-1, 4-benzoxazin-6-yl)(1-naphtalenyl)methanone monomethanesulfonate), N-arachidonyl ethanolamide (anandamide) and the mu and kappa opioid receptor agonists heroin and U69593, alone and in conjunction with a cannabinoid receptor antagonist, SR 141716A [N-(piperidin-1-1-yl)-5-(4-chlorophenyl)-1(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] and an opioid receptor antagonist, quadazocine, in rhesus monkeys (Macaca mulatta). Using 12 adult rhesus monkeys, latencies to remove the tail from a 50 degrees C water bath, respiration in 5% CO2 and heart rate were measured. When administered alone, SR 141716A (1.8, 5.6 mg/kg i.m.) did not alter nociception, respiration or heart rate. Delta-9-THC (0.1-10 mg/kg i.m.) and WIN 55212 (0.1-10 mg/kg i.m.) dose-dependently increased antinociception and dose-dependently decreased respiratory minute and tidal volumes and heart rate. These antinociceptive, respiratory and heart rate effects were reversed by SR 141716A but not by the opioid antagonist quadazocine (1 mg/kg i.m.). Anandamide (10 mg/kg i.m.) also produced antinociception. Heroin (0.01-10 mg/kg i.m.) and U69593 (0.01-3.2 mg/kg i.m.) also dose-dependently increased antinociception and decreased respiratory and heart rate measures; these effects were antagonized by quadazocine but not by SR 141716A. These results demonstrate selective and reversible antagonism of cannabinoid behavioral effects by SR 141716A in rhesus monkeys.

Analgesics, Opioid↗
PubMed1997

Efficacy and safety of one year of growth hormone therapy in steroid-dependent nephrotic syndrome.

OBJECTIVES: To study the efficacy and safety of 1 year of growth hormone (GH) therapy in children with steroid-dependent nephrotic syndrome. STUDY DESIGN: A prospective pilot, open study in which GH (mean dose 0.32 mg/kg per week) was administered for 1 year to 8 children with steroid-dependent nephrotic syndrome requiring prednisolone (mean dose 0.46 mg/kg per day) to maintain remission. Steroid dependence was defined as recurrence of proteinuria within 2 weeks of discontinuation of prednisolone, or when the dose was lowered below a critical level. At entry, all patients had been steroid dependent for at least 1 year. Anthropometric and bone mineral density measurements after treatment were compared with 1-year pretreatment data. RESULTS: Pretreatment mean (+/-SD) chronologic age was 12.6 (+/-3.1) years, with a mean bone age of 9.1 (+/-2.0) years, with delayed puberty in five patients. The mean height velocity increased from 3.7 (+/-1.4) to 9.4 (+/-2.1) cm/yr after 1 year of treatment (p < 0.05). The mean height standard deviation score increased from -1.4 (+/-1.6) to -0.3 (+/-1.1), (p < 0.05). In the spine, the mean bone mineral density increased from 0.50 to 0.64 gm/cm2 (p < 0.05), and in the femoral neck, from 0.55 to 0.64 gm/cm2 (p < 0.05) after 1 year of treatment. Mean lean body mass increased from 58.1% to 62.6% (p < 0.01). There were no significant changes in creatinine clearance, fasting glucose, fasting insulin, or glycosylated hemoglobin levels. The mean bone age increased to 11.4 (+/-2.4) years, and pubertal stage advanced in 2 patients. CONCLUSIONS: One year of GH therapy is effective in improving the height standard deviation score, height velocity, bone mineral density, and lean body mass of children with steroid-dependent nephrotic syndrome. There were no significant adverse effects. However, the bone age accelerated at a greater pace than the height age, and further studies are required to define the role of GH therapy in steroid-dependent nephrotic syndrome.

Adolescent↗
PubMed1997

Selecting nursing home residents for satisfaction surveys.

Many cognitively impaired nursing home (NH) residents are excluded from interviews measuring quality of life or care based on the belief that these residents cannot accurately answer questions. These exclusions are based on subjective criteria and ignore individual differences among cognitively impaired NH residents. This study describes a screening rule based on four minimum data set (MDS) indicators that provides an objective method for identifying residents capable of accurate report. Sixty percent of a sample of 83 NH residents who could answer yes or no questions about their care could do so accurately. Eighty-one percent of the sample was correctly classified by the MDS indicators.

Aged↗
PubMed1997

Induction of spermatogenesis in isolated hypogonadotrophic hypogonadism with gonadotrophins and early intervention with intracytoplasmic sperm injection.

Idiopathic hypogonadotrophic hypogonadism (IHH) is a potentially correctable cause of male infertility. However hormonal treatment is usually a slow process and artificial reproductive techniques such as intracytoplasmic sperm injection (ICSI) might be resorted to before full testicular response has been achieved. We report here an unusual variant of IHH of post-pubertal onset in which early intervention with ICSI was attempted. Our patient was 37 years old and presented with male infertility due to azoospermia and undetectable serum gonadotrophin concentrations. He had an apparently normal pubertal development, a testicular volume of 8 ml, normal pituitary-thyroid and pituitary-adrenal function, as well as normal computerized tomographic appearance of the sella region. A combination of human chorionic gonadotrophin (HCG) and menopausal gonadotrophins (HMG) was administered. Spermatozoa were first detected in the semen after 3 months and reached a concentration of approximately 2x10(6)/ml after 9 months. ICSI was attempted at this point; the spermatozoa had good fertilizing ability and three embryos were obtained and replaced. Unfortunately no pregnancy resulted. Treatment with 5000 IU HCG and 150 IU HMG three times per week was continued and sperm counts rose rapidly thereafter to reach 28.3x10(6)/ml after 16 months of injections. His wife conceived naturally during this period and the pregnancy is now in the second trimester. This case illustrates the good prognosis of the rare patient with IHH of post-pubertal onset when treated with gonadotrophins, and suggests that ICSI procedures should be delayed until final testicular maturation is attained.

Adult↗
PubMed1997

Impact of psychosocial factors on health outcomes in the elderly. A prospective study.

One hundred and thirty-five initially healthy men and women older than 65 years of age were studied prospectively to identify factors associated with health outcomes. At study onset, measures of personality, social interaction, and health locus of control were obtained while participants were still healthy. A reliable health outcome measure was developed, based on the annual objective coding of morbidity. Correlations between variables showed significant associations between age, a less independent personality trait, and poor health outcomes. Anxiety and low levels of social interaction were associated with poor health after 8 years. Gender and health locus of control were not significantly related to health outcomes. A path analysis showed significant direct paths between age and trait anxiety and 8-year health outcomes, and indirect paths between anxiety and extroversion and 8-year health, by way of social interaction. There was no evidence that social interaction mediated the effects of either anxiety or extroversion on health. The structure of psychosocial characteristics of the healthy elderly sample was revealed in the pattern of correlations between personality, social interaction, and locus of control.

Aged↗
PubMed1996

Isolation of an additional soybean cDNA encoding Ypt/Rab-related small GTP-binding protein and its functional comparison to Sypt using a yeast ypt1-1 mutant.

We have previously reported the isolation of a gene from a soybean cDNA library encoding a Ypt/Rab-related small GTP-binding protein, Sypt. Here, we report the isolation of a second Ypt/Rab-related gene, designated Srab2, from the same soybean cDNA library. And we compare the in vivo function of the two soybean genes utilizing a yeast ypt1-1 mutant. The Srab2 gene encodes 211 amino acid residues with a molecular mass of 23 169 Da. The deduced amino acid sequence of the Srab2 is closely related to the rat (76%) and human (75%) Rab2 proteins, but it shares relatively little homology to Sypt (46%) and Saccharomyces cerevisiae ypt proteins (41%). Genomic Southern blot analysis using the cDNA insert of Srab2 revealed that it belongs to a multigene family in the soybean genome. The protein encoded by Srab2 gene, when expressed in Escherichia coli, disclosed a GTP-binding activity. The expression pattern of the Srab2 gene is quite different from that of the Sypt gene. The Srab2 gene is predominantly expressed in the plumule region, while expression was very low in the other areas in soybean seedlings. On the other hand, the Sypt mRNA is not detectable in any tissues of soybean seedlings grown in the dark. However, light significantly suppressed the Srab2 gene expression, but enhanced the transcript levels of the Sypt gene in leaf and, at even higher levels, in root tissues. When the Srab2 and Sypt genes are introduced separately into a S cerevisiae defective in vesicular transport function, the Srab2 gene cannot complement the temperature-sensitive yeast ypt1-1 mutation at all, in contrast to the Sypt gene. In conclusion, the difference of functional complementation of the yeast mutation together with differential expression of the two genes suggest that the in vivo roles of the Srab2 and Sypt genes may be different in soybean cells.

Amino Acid Sequence↗