Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 595 records · Page 33Linked to original sources

PubMed1999

Endotoxin stimulates nitric oxide production in the paraventricular nucleus of the hypothalamus through nitric oxide synthase I: correlation with hypothalamic-pituitary-adrenal axis activation.

Nitric oxide (NO) is an unstable gas that is produced in brain tissues involved in the control of the activity of the hypothalamus-pituitary-adrenal (HPA) axis. Transcripts for constitutive neuronal NO synthase (NOS I), one of the enzymes responsible for NO formation in the brain, is up-regulated by systemic endotoxin [lipopolysaccharide (LPS)] injection. However, this change is delayed compared with LPS induced-ACTH release, which makes it difficult to determine whether it is functionally important for the hormonal response. To obtain a more resolutive time course of the NO response, we first measured NO in microdialysates of the paraventricular (PVN) nucleus of the hypothalamus. The iv injection of 100 microg/kg LPS induced a rapid and short-lived increase in concentrations of this gas, which corresponded to the initiation of the ACTH response. LPS-induced Ca2+-dependent NOS activity in the PVN as well as the number of PVN cells expressing citrulline (a compound produced stoichiometrically with NO) also increased significantly over a time course that corresponded to ACTH and corticosterone release. Finally, blockade of NO production with the arginine derivative Nomega-nitro-L-argininemethylester (L-NAME; 50 mg/kg, sc), which attenuated the ACTH response to LPS, virtually abolished basal NOS activity in the PVN, as well as anterior and neurointermediate lobes of the pituitary, and prevented the appearance of citrulline in the PVN of rats injected with LPS. Collectively, these results show that LPS-induced activation of the HPA axis correlates with the activation of the PVN NOergic system, and supports a stimulatory role for NO in the modulation of the HPA axis in response to immune challenges.

Adrenal Glands↗

PubMed1999

CRF type I receptor-deficient mice exhibit a pronounced pituitary-adrenal response to local inflammation.

Recent studies indicate that the regulation of adrenocorticotropin (ACTH) secretion by corticotropin-releasing factor (CRF) is mediated predominantly by the type I CRF receptor (CRF-R1). Indeed, CRF-R1-deficient (CRF-R1 -/-) mice show marked impairment of the pituitary-adrenal axis. However, the plasma ACTH concentrations of unstressed CRF-R1 -/- mice are similar to those in wild-type mice. We show here that arginine vasopressin (AVP) is a major ACTH secretagogue in CRF-R1 -/- mice in resting conditions, since administration of anti-AVP serum, but not anti-CRF serum, markedly reduced (by 60%) resting plasma ACTH concentrations in these mutants. We also investigated the pituitary-adrenal response to turpentine-induced local inflammation in CRF-R1 -/- mice. Administration of turpentine into the hind-limb of CRF-R1 -/- mice produced a slightly (15-25%) smaller swelling of the limb, but a 10 fold greater rise in plasma IL-6 levels, compared to CRF-R1 +/+ controls. Turpentine-induced local inflammation produced pronounced elevations in the plasma concentrations of both ACTH and corticosterone in both CRF-R1 -/- and wild-type mice, but ACTH secretion could be inhibited by anti-CRF and anti-AVP sera only in wild-type mice. These data indicate that resting ACTH secretion in CRF-R1 -/- mice is in part attributable to AVP-dependent mechanisms. Furthermore, while in normal mice the pituitary-adrenal response to local inflammation is mediated largely via CRF-dependent mechanisms, mice deficient in CRF-R1 are still able to mount a pituitary-adrenal response via mechanisms that do not depend critically on either CRF or AVP action.

Adrenocorticotropic Hormone↗

PubMed1999

Development of a luminescent bioassay for thyroid stimulating antibodies.

The hyperthyroidism of Graves Disease (GD) is due to thyroid stimulating antibodies (TSAb) which are thyrotropin (TSH) agonists. They are detected routinely by measuring their ability to inhibit TSH binding to the receptor (TBII), which does not reflect their true biological activity. Current bioassays which measure cAMP by RIA, are not suitable for routine use. We have developed a luminescent bioassay for TSAb, by introducing a cAMP responsive luciferase construct into CHO cells stably expressing the human TSH receptor (TSHR). Clone lulul displays dose dependent TSH response detectable from 10 microU/ml and maximal at 10 mU/ml when a >25 fold increase in light output is obtained. 34 euthyroid sera were tested to determine a reference range, with values >1.5 relative light units (R.L.U.) being considered positive. An international TSAb standard responded in a dose dependent manner with 10 mIU/ml giving an R.L.U. of >10. The assay was adapted to a 96 well format for automatic readout and 100 treated GD samples (50 TBII negative and 50 TBII positive) were tested, 73% being positive. In contrast only 4% of 79 control sera from individuals with Hashimoto's, non-thyroid autoimmunity or multinodular goitre produced R.L.U. >1.5. When 44 of the GD sera were compared in a traditional salt-free bioassay, 61% were positive compared with 75% in the new luminescent assay. In conclusion, we have developed a luminescent bioassay for TSAb, using unfractionated serum which is capable of high throughput suitable for routine use.

Animals↗

PubMed1999

Studies of the chemical structure of gangliosides in deer antler, Cervus nippon.

The biological activity of deer antler has been considered to originate in the gangliosides, although the structures of gangliosides have not been well elucidated. The quality of deer antler as an Asian folk medicine has often been evaluated by the amount of gangliosides contained in the crude drug. We have completed the structural determination of five gangliosides isolated from deer antler in the present study. Five ganglioside fractions were isolated and purified from deer antler, Cervus nippon, by the Folch-Suzuki partition method, DEAE-Sephadex A-25, and further by silica gel column chromatography. High field proton nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and fast atom bombardment-mass spectrometry studies characterized the isolated ganglioside fractions. GM3 and GD3 were present in the isolated ganglioside fractions. Samples were hydrolyzed in trifluoroacetic acid for direct compositional analysis and analyzed for sialic acid and neutral sugar without prior derivatization. Separation of the monosaccharides was achieved by HPLC on a Dionex CarboPac column eluted at a high pH. The resolved monosaccharides were identified using standard monosaccharides by pulsed amperometric detection. N-Acetyl GM3 (Neu5Ac), N-glycolyl GM3 (Neu5Gc), and N-acetyl GD3 (Neu5Ac) were present in the antler. The major ceramide moiety was composed of C16:0 or C22:0 fatty acids along with either C18 sphingosine or C20 eicosasphingosine.

Animals↗

PubMed1999

Increased susceptibility to measles in infants in the United States.

BACKGROUND: Women born in the United States after measles vaccine licensure in 1963 transfer less measles antibody to their infants than do older women. This may result in increased susceptibility to measles among infants. OBJECTIVE: To determine the effect of maternal year of birth on the risk for measles in infants. METHODS: We enrolled 128 unvaccinated infants </=15 months of age who had documented exposure to measles from 1990 through 1992 in a retrospective cohort study. We interviewed their mothers by telephone to obtain demographic data, medical and vaccination history, and details of measles exposure and outcome. We used logistic regression analysis to estimate the effect of maternal year of birth. RESULTS: Infants whose mothers were born after 1963 had a measles attack rate of 33%, compared with 12% for infants of older mothers. In logistic regression analysis, the adjusted odds ratio for maternal year of birth (born after 1963) was 7.5 (95% confidence interval 1.8, 30.6). Other significant risk factors were older infant age, mothers who developed measles after delivery, and exposure within 2 days of the rash onset of the exposing case. CONCLUSIONS: Infants whose mothers were born after 1963 are more susceptible to measles than are infants of older mothers. An increasing proportion of infants born in the United States may be susceptible to measles. Infants at high risk of exposure to measles should be vaccinated at 12 months of age. Vaccination programs that reduce transmission of the measles virus in the general population reduce the risk of infant exposure to measles.

Age Distribution↗

PubMed1999

Retinopathy of prematurity in the 1990s.

Infants diagnosed with retinopathy of prematurity (ROP) are at risk for developing visual impairments. The International Classification of ROP (ICROP) developed the most useful tool available for communicating the location and extent of the condition, with three zones to describe the location and five stages to describe the extent. Despite current knowledge and treatment, however, 500 infants are blinded each year by ROP. Infants at highest risk are the smallest and most immature. The nurse must understand why and how ROP occurs and the forms of management used to treat ROP. This article reports on the incidence, pathophysiology, risk factors, screening, treatment, and long-term complications of ROP in the 1990s.

Blindness↗

PubMed1999

Functional roles of the proprioceptive system in the control of goal-directed movement.

This article explored functional roles of the proprioceptive system during the control of goal-directed movements. Proprioceptive information contributes to the control of movement through both reflex and central connections. Spinal and transcortical reflex loops establish a servomechanism which provides automatic corrections of unexpected changes in muscle length and allows compensation for undesirable irregularities in the mechanical properties of muscles by modulating limb stiffness at the subconscious level. Central connections provide the control system with information about peripheral states which is used in voluntary components of movement control. Before the initiation of movement, proprioceptive information about initial limb orientation becomes a basis for the programming of motor commands. During a movement, proprioceptive input about velocities and angular displacements of a limb is used to regulate movement by triggering planned sequences of muscle activation and modulating motor commands. After movement, feedback produced by responses is compared with previously stored information, verifying the quality of the movement. Considering potential roles of the reflex and central connections, the proprioceptive system seems to constitute an important aspect of motor control mechanisms, providing the control system with efficiency and flexibility in the regulation of goal-directed movements.

Biomechanical Phenomena↗

PubMed1999

Absence of evidence of Borna disease virus infection in Swedish patients with Chronic Fatigue Syndrome.

Chronic Fatigue Syndrome (CFS) is characterized by debilitating fatigue, somatic symptoms and cognitive impairment. An infectious basis has been proposed; candidate agents include enteroviruses, herpesviruses, retroviruses and Borna disease virus (BDV), a novel neurotropic virus associated with neuropsychiatric disorders. Sera and peripheral blood mononuclear cells (PBMC) from Swedish CFS patients were assayed for evidence of infection using ELISA and Western immunoblot for detection of antibodies to BDV proteins N, P and gp18; and using nested reverse transcriptase polymerase chain reaction (RT-PCR) for detection of BDV N- and P-gene transcripts. No specific immunoreactivity to BDV proteins was found in sera from 169 patients or 62 controls. No BDV N- or P-gene transcripts were found through RT-PCR analysis of PBMC from 18 patients with severe CFS. These results do not support a role for BDV in pathogenesis of CFS.

Adult↗

PubMed1999

Effects of exposure conditions to footshocks early in life on spontaneous locomotor activity at maturity in rats.

Both genetic and environmental factors are involved in establishing a behavior. An animal study was done to determine the characteristics of interaction between genetic (nature) and environmental (nurture) factors. Delivery of footshocks (0.8 mA x 60 times, at random) early in life was used as the environmental stimulus. As the footshock was delivered repeatedly, a rat showed helplessness behavior and the number of shocks necessary to elicit helplessness was measured to quantify the trait of an animal in coping with the aversive environmental stimulus. The nocturnal ambulatory activity at adulthood was measured as a behavioral expression of the nature-nurture interaction. Although the experience of footshocks early in life did not significantly alter average activity levels at adulthood, the activity was positively correlated with the number of shocks necessary to elicit helplessness (nature) while receiving footshocks (nurture) on postnatal day 14. Additionally, a second exposure to identical shock parameters on postnatal day 21 reversed the relationship. These results clearly showed that an interaction between nature and nurture during infancy leads to substantial behavioral alterations later in life, and suggest that the nature-dependent determination of an adult behavior can be modified in different directions by the conditions of an environmental experience early in life.

Aging↗

PubMed1999

Behçet's disease sera containing antiendothelial cell antibodies promote adhesion of T lymphocytes to cultured human dermal microvascular endothelial cells.

Antiendothelial cell antibodies (AECA) have been detected in the sera of patients of autoimmune diseases showing vasculitis. Using IgM-ELISA, we found AECA in 42 (56%) of 75 sera samples from patients with Behçet's disease in a previous study. All of the 15 AECA-positive sera of Behçet's disease patients had an increased expression of the intercellular cell adhesion molecule-1 (ICAM-1), 93.3% of the sera induced the vascular cell adhesion molecule-1 (VCAM-1), and 100% of the serum induced the E-selectin molecule on human dermal microvascular endothelial cells (HDMEC). After stimulation of HDMEC with AECA-positive sera of Behçet's disease patients, the expression of ICAM-1 and VCAM-1 on HDMEC increased significantly at 4 hours, reaching a peak at 16 hours. Expression of E-selectin was induced at 1 hour after stimulation with a peak at 4 hours and it decreased thereafter. Adherence of T lymphocytes to HDMEC increased significantly after stimulation with AECA-positive sera from Behçet's disease patients. Also, the adherence of T lymphocytes to HDMEC increased at 4 hours and returned to its normal level at 48 hours. These results show that AECA-positive sera of Behçet's disease patients are capable of activating HDMEC to promote the adherence of T lymphocytes to increase the expression of ICAM-1, VCAM-1, and E-selectin on the cell surfaces. The whole process may play an important role in the pathogenesis of vasculitis in Behçet's disease.

Antibodies↗

PubMed1999

Noninvasive approaches to peripheral vascular disease. What's new in evaluation and treatment?

Current availability of noninvasive evaluation and treatment methods for peripheral vascular disease is unprecedented. Understanding of vascular and molecular biology, physiology, and pathology has improved significantly, as have the technologic capabilities of ultrasonography, digital imaging, therapeutic angiogenesis, and other methods not even in existence a few decades ago. However, although science continues to advance rapidly on multiple fronts and, eventually, noninvasive methods will supersede current treatment options, for the immediate future, heavy emphasis should continue to be on preventive strategies.

Genetic Therapy↗

PubMed1999

High O6-methylguanine methyl transferase activity is frequently found in human oral cancer cells with p53 inactivation.

Many studies have indicated that cancer cells expressing mutant (mt) p53 are resistant to genotoxic stress such as chemotherapy and radiation therapy. Inasmuch as most human oral cancer cells either express mt p53 or are infected with human papillomavirus (HPV), we determined the sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a genotoxic chemical carcinogen, the activity of a DNA repair enzyme O6-methylguanine methyl transferase (MGMT) and the status of p53 in 11 human oral cancer cell lines, 2 HPV-immortalized human oral keratinocytes and 3 normal human oral keratinocyte (NHOK) cultures. Ten cancer cell lines demonstrated significantly higher level of MGMT activities compared to normal or immortalized non-tumorigenic cells, while one cancer cell line showed negligible MGMT activity. All immortalized cells and NHOK showed very low MGMT activity. Interestingly, all cancer cells with high MGMT activity expressed either mt p53 or harbored HPV DNA. However, infection of one cancer cell line (that does not demonstrate the MGMT activity) with retrovirus expressing an mt p53 protein did not alter the sensitivity of cells to MNNG and the enzyme activity. These data indicate that most human oral cancer cells contain moderately high DNA repair enzyme activity, and in doing so may be resistant to genotoxic stress, but the association of p53 with MGMT activities should further be investigated.

Blotting, Western↗

PubMed1999

A case of primary leiomyosarcoma of the lesser omentum.

Leiomyosarcoma is a rare tumor that originates in the smooth muscle, usually in the gastrointestinal tract, the retroperitoneum and the genitourinary tract. The omentum has been rarely reported as a primary site of occurrence with leiomyosarcoma. A 72 year-old woman, with palpable mass on the left upper quadrant of abdomen and weight loss, was admitted to St. Paul's Hospital. Abdominal CT scan showed a 12 x 8 x 8 cm-sized cystic mass in the left upper quadrant of the abdomen. Endoscopic ultrasonography showed a large cystic mass between the stomach and the liver, which was 1.6 cm length in wall thickness. Laparotomy and resection of the mass was performed. A 12 x 8 x 8 cm-sized mass, originated from the lesser omentum, was discovered near the lesser curvature of the stomach. Microscopic examination revealed spindle-shaped cells with 7-8 mitoses per high power field. She was diagnosed as primary leiomyosarcoma originated from the lesser omentum.

Aged↗

PubMed1999

[Evaluation of frozen section diagnosis of parotid gland tumors].

A retrospective study is presented comparing the results of 167 frozen section diagnoses of surgical extirpated parotid gland tumors with permanent-section diagnoses. Percentages of correct diagnosis for malignancy (cases correctly classified as benign or malignant tumors) and of correct diagnosis for histopathology (cases in which frozen section diagnosis and permanent-section diagnosis were identical) were calculated. Percentages of correct diagnosis for malignancy in all cases, benign cases, and malignant cases were 98.8%, 99.3%, and 95.8%, respectively. Percentages of correct diagnosis for histopathology in all cases, benign cases, and malignant cases were 94.0%, 97.2%, and 75.0%, respectively. These results are superior to the previous reports both of frozen section diagnosis and of fine-needle aspiration biopsy diagnosis although the data for histopathological diagnosis in malignant tumors are average compared to previous reports. We conclude that diagnoses of most parotid gland tumors based on frozen section examination are reliable and accurate, but caution should be exercised in malignant tumors diagnosis.

Biopsy, Needle↗

PubMed1999

[3H]gemcitabine uptake by nucleoside transporters in a human head and neck squamous carcinoma cell line.

Cellular uptake of many chemotherapeutic nucleoside analogs is dependent on the activity of a family of nucleoside transport proteins located in the cell plasma membrane. In the present study, we examined the role of these transporters in the accumulation of gemcitabine by a human head and neck squamous carcinoma cell line. The uptake of [3H]gemcitibine was compared with that of [3H]uridine and [3H]formycin B in the parent cell line (HN-5a) and in a gemcitabine-resistant variant (GEM-8e). The HN-5a and GEM-8e cells were similar in their transport characteristics and expressed predominantly the es (equilibrative, inhibitor-sensitive) transporter subtype; less than 10% of the influx of [3H]formycin B or [3H]uridine was mediated by the ei (equilibrative inhibitor-resistant) system, and there was no evidence for Na+-dependent nucleoside transporters. [3H]Gemcitabine (10 microM) entered these cells via both the es and ei transporters with an initial rate of uptake similar to that seen with the use of [3H]formycin B or [3H]uridine. In addition, ATP-replete cells accumulated significantly less [3H]gemcitabine than did ATP-depleted cells, which is indicative of an active efflux mechanism for gemcitabine. These results show that gemcitabine is a substrate for both the es and ei nucleoside transporters of HN-5a and GEM-8e cells and that gemcitabine resistance of the GEM-8e cells cannot be attributed to changes in transporter activity. Further studies to define the characteristics of the putative efflux mechanism are clearly warranted because this system has the potential to significantly affect the clinical efficacy of gemcitabine.

Adenosine Triphosphate↗

PubMed1999

Circulating levels of beta-chemokines in systemic lupus erythematosus.

OBJECTIVE: Recent evidence suggests the role of beta-chemokines and their receptors in human immunodeficiency virus infection. We examined the serum levels of beta-chemokines in patients with systemic lupus erythematosus (SLE). METHODS: The serum levels of beta-chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES, and monocyte chemoattractant protein-1 (MCP-1) in patients with SLE were determined by ELISA. RESULTS: There were significant differences between the patients with SLE and healthy controls in the serum concentrations of RANTES (p < 0.001) and MCP-1 (p < 0.01), but not MIP-1alpha (p = 0.07) and MIP-1beta (p = 0.68). A decrease of RANTES and an increase of MCP-1 was observed with the progression of disease activity in the patients with SLE. CONCLUSION: Changes in the serum levels of RANTES and MCP-1 may indicate an interaction between SLE disease activity and the production of beta-chemokines.

Adolescent↗

PubMed1999

Ethyl linoleate in meconium: a biomarker for prenatal ethanol exposure.

BACKGROUND: Fetal alcohol syndrome, fetal alcohol effects, alcohol-related neurodevelopmental disorder, and alcohol-related birth defects, all terms referring to the spectrum of consequences of in utero exposure to ethanol, are a major public health burden. There is currently no laboratory test to identify newborns exposed to ethanol in utero. Meconium was analyzed for ethyl linoleate, a metabolite of ethanol, as a biological marker for fetal ethanol exposure. METHODS: Samples of meconium were obtained from 248 infants and analyzed for fatty acid ethyl esters. Detailed maternal alcohol, tobacco, and drug use histories were obtained within 1 month of giving birth. RESULTS: The detection of ethyl linoleate in meconium was called a positive test. The mean number of drinks reported per week in the month before pregnancy, the first trimester, and overall were significantly higher in the positive group (unadjusted: 9.2 +/- 1.9 vs. 4.3 +/- 1.4, p = 0.004; 7.3 +/- 1.7 vs. 3.8 +/- 1.2, p = 0.03; and 6.1 +/- 1.3 vs. 3.0 +/- 1.0, p = 0.006). A positive test was not associated with marijuana, cocaine, or tobacco use. Sensitivity and specificity of the test were 72% and 51% to distinguish women who reported 1 or more drinks/week in the third trimester from women who denied use, and 68% and 48% to distinguish women who used > or =1 drink/week from women who used <1 drink/week in the month before pregnancy. CONCLUSIONS: The presence of ethyl linoleate in meconium is the first reported biological marker for maternal ethanol use during pregnancy. Because of the inherent inaccuracy associated with the use of self-reporting, the establishment of true values of sensitivity and specificity will require validation where the presence, quantity, and timing of exposure to alcohol is known. Further validation of this marker will permit identification and intervention of at-risk infants.

Adult↗

PubMed1999

RNA-dependent RNA polymerase activity associated with Eimeria necatrix virus particles containing either double-stranded or single-stranded RNA.

Single-stranded (ss) RNA containing and double-stranded (ds) RNA containing virus particles of Eimeria necatrix were isolated by centrifugation through a CsCl gradient. RNA from the gradient fractions was identified as single-stranded or double-stranded by probing northern blots with digoxigenin-labeled riboprobes. These probes were generated with SP6 and T7 RNA polymerases from a partial cDNA clone derived from 5.6-kb viral dsRNA of E. necatrix. RNA-dependent RNA polymerase (RDRP) activity was identified in these CsCl-purified virus particles. The polymerase products of the ssRNA particles consisted of dsRNA indicating replicase activity, whereas the polymerase products of the dsRNA particles consisted of ssRNA indicating transcriptase. activity. RNase treatment in high salt solution (0.3 M NaCl) of the pooled RDRP products revealed that the products consisted of both RNase-resistant dsRNA and RNase-sensitive ssRNA. These results show that both replicase and transcriptase activities were present in the purified virus. The digoxigenin-labeled products hybridized to both SP6 and T7 transcripts confirming the presence of both activities.

Animals↗