Assignment of the rat calcineurin inhibitor gene (Cain) to rat chromosome band 20p12 by fluorescence in situ hybridization.
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Animals↗
Biomedical subjects
H Kim
Publications and source records attributed to H Kim.
Modulation of IL-18 production in the adrenal cortex following acute ACTH or chronic corticosterone treatment.
Interleukin (IL)-18 is a proinflammatory cytokine and a stimulator of cell-mediated immune responses. We have previously reported that acute stress stimulates the production of IL-18 mRNA in the glucocorticoid (GC)-producing cells of the adrenal cortex. In order to investigate the mechanisms governing the expression of IL-18 in the adrenal cortex, the effects of acute ACTH or chronic corticosterone treatment on the levels of IL-18 mRNA and protein were examined by in situ hybridization and Northern and Western blot assays. Adult male Sprague-Dawley rats received a subcutaneous injection of ACTH or subcutaneous implantation of slow-release corticosterone pellets followed by an injection of saline or ACTH. After 4 h, ACTH induced a 4-fold increase in IL-18 mRNA levels and elevated the content of pro-IL-18 peptide. Six days of chronic corticosterone treatment did not alter the basal levels of IL-18 mRNA and reduced those of pro-IL-18. Finally, ACTH treatment of animals under the corticosterone regimen induced a 2-fold increase in IL-18 mRNA and elevated the levels of the pro-IL-18 protein. The levels of the precursor, p45, and the active subunit p10 peptides of the IL-18-processing enzyme, IL-1beta-converting enzyme (ICE), showed no substantial differences in all the conditions tested. IL-1beta was not detected under these experimental conditions. These data demonstrate that the production of IL-18 in the adrenal cortex is stimulated by ACTH treatment and is not inhibited by the direct action of corticosterone. In contrast to the anti-inflammatory action of GCs, IL-18 may have an immunostimulatory role during acute stress.
Adrenal Cortex↗
Perceived motion in complementary afterimages: verification of a neural network theory.
Steady fixation of a regular pattern like a bar grating or concentric circles leads to a complementary afterimage at pattern offset. The afterimage has the appearance of shimmering lines that are locally orthogonal to the orientations of the inducing image. Additionally, the afterimage includes motion running parallel to the orientation of the afterimage lines. We argue that this afterimage motion supports the existence of a cue to motion that is based on the spatial organization of oriented responses. This cue was previously proposed after analysis of a neural network model of visual perception. We test predictions of the model on various types of complementary afterimage inducing stimuli. When a contrast or size gradient is included in the inducing image, the afterimage motion moves toward the higher part of the gradient, in agreement with the model. Implications of this cue for computational and neurophysiological theories of motion perception are discussed.
Figural Aftereffect↗
Distribution of obstructive intimal lesions and their cellular phenotypes in chronic pulmonary hypertension. A morphometric and immunohistochemical study.
We investigated the distribution of pulmonary arteriopathy in chronic pulmonary hypertension (PH) in a quantitative histopathologic study, using computer-assisted image analysis. We also examined the histologic manifestations and cellular phenotypes of various obstructive intimal lesions in PH with an immunohistochemical method. A total of 53 lungs removed at autopsy or explantation were obtained for the study from 51 documented cases of moderate to severe PH (15 cases of primary pulmonary hypertension [PPH], eight cases of Eisenmenger's syndrome [EISEN], 22 cases of chronic major-vessel thromboembolic disease [CTED], and three cases of PH associated with other known causes), and two unused donor lungs served as normal controls. Intimal thickening in PPH was most prominent in small pulmonary arteries and arterioles less than 200 micrometer in diameter. Plexiform lesions in PPH were associated with significantly smaller arteries than in EISEN. Arteries larger than 400 micrometer showed a significant intimal thickening only in CTED. Obstructive intimal lesions in PH comprised a morphologic spectrum with frequent intermediate forms between plexiform and thrombotic lesions. Most cells within various intimal lesions showed an immunoprofile of myofibroblasts that were positive for vimentin and alpha-smooth muscle actin, but negative for desmin and endothelial markers including Factor VIII, clonal designator (CD)31, and CD34. Endothelial markers were positive only in the single layer of cells lining slitlike lumens, when the latter were present. In conclusion, major types of PH had characteristic distribution patterns of obstructive intimal lesions, showing mainly a myofibroblastic phenotype and variable endothelial/vascular differentiation.
Adult↗
Sleep fragmentation, awake blood pressure, and sleep-disordered breathing in a population-based study.
Arousal from sleep produces transient increases in systemic blood pressure, leading to the suggestion that repeated arousals are associated with a sustained increase in daytime blood pressure. Using data from the Wisconsin Sleep Cohort Study, a population-based study, we tested the hypothesis that sleep fragmentation is associated with elevated awake blood pressure. Sleep, breathing, and seated blood pressure measurements from 1,021 participants (age 42 +/- 8 yr; 590 males) were analyzed. Sleep fragmentation was defined as the total number of awakenings and shifts to Stage 1 sleep divided by the total sleep time (sleep fragmentation index: SFI). To reduce the confounding influence of sleep-disordered breathing, which is related to both increased daytime blood pressure and sleep fragmentation, all participants with an apnea-hypopnea index (AHI) > or = 1 were analyzed separately. Accounting for the influences of sex, age, body mass index, and antihypertensive medication use, the SFI was significantly associated with higher levels of awake systolic blood pressure in people with an AHI < 1; a 2 standard deviation increase in the SFI was associated with a 3.1 mm Hg rise in awake systolic blood pressure. In participants with an AHI > or = 1, there was no independent association between the SFI and awake blood pressure after controlling for the influence of the AHI.
Adult↗
Surveillance for recurrent head and neck cancer using positron emission tomography.
PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P =.013) or PE (P =.002) in the detection of recurrence. CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.
Antineoplastic Combined Chemotherapy Protocols↗
Thyrotropin modulates interferon-gamma-mediated intercellular adhesion molecule-1 gene expression by inhibiting Janus kinase-1 and signal transducer and activator of transcription-1 activation in thyroid cells.
TSH is known as an important hormone that plays the major role not only in the maintenance of normal physiology but also in the regulation of immunomodulatory gene expression in thyrocytes. The adhesion molecule intercellular adhesion molecule-1 (ICAM-1) was identified as one of the proteins that are abnormally expressed in the thyroid gland during autoimmune thyroid diseases. In this study we found that TSH inhibits interferon-gamma (IFNgamma)-mediated expression of the ICAM-1 gene, and we investigated the involved mechanisms in rat FRTL-5 thyroid cells. After exposure to IFNgamma, ICAM-1 expression is positively regulated at the level of transcription. This effect occurs via the IFNgamma-activated site (GAS) element in the ICAM-1 promoter as a consequence of the activation of STAT1 (signal transducer and activator of transcription-1), but not of STAT3. On the other hand, after exposure to TSH plus IFNgamma, ICAM-1 transcription is negatively modulated. We found that this inhibitory effect of TSH also occurs via the GAS element. Electrophoretic mobility shift assays confirmed that the IFNgamma-induced DNA-binding activities of STAT1 were reduced by TSH. Furthermore, our results showed that the inhibitory effect of TSH on IFNgamma signaling is caused by inhibition of tyrosine phosphorylation on STAT1, Janus kinase-1 (Jak1), and IFNgamma receptor a, but not Jak2. In conclusion, we have identified a novel mechanism in which TSH modulates the IFNgamma-mediated Jak/STAT signaling pathway through the inhibition of Jak1 and STAT1.
Animals↗
Changes in insulin-like growth factor-binding protein-3 messenger ribonucleic acid in endothelial cells of the human corpus luteum: a possible role in luteal development and rescue.
In the human menstrual cycle, extensive angiogenesis accompanies luteinization; and the process is physiologically important for corpus luteum (CL) function. During luteolysis, the vasculature collapses, and the endothelial cells die. In a conceptual cycle, the CL persists both functionally and structurally beyond the luteoplacental shift. Although luteal rescue is not associated with increased angiogenesis, endothelial survival is extended. Despite the central role of the luteal vasculature in fertility, the mechanisms regulating its development and demise are poorly understood. There is increasing evidence that insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important effectors of luteal function. Here, we have found that IGFBP-3 messenger RNA is expressed in the endothelium of the human CL and that the levels of message change during luteal development and rescue by human CG. The signal was strong during the early luteal phase, but it showed significant reduction during the mid- and late luteal phases. Interestingly, administration of human CG caused a marked increase in the levels of IGFBP-3 messenger RNA in luteal endothelial cells that was comparable to that observed during the early luteal phase. We conclude that endothelial cell IGFBP-3 expression is a physiological property of the CL of menstruation and pregnancy. These observations raise the intriguing possibility that the regulated expression of endothelial IGFBP-3 may play a role in controlling angiogenesis and cell responses in the human CL by autocrine/paracrine mechanisms.
Adult↗
Thyrotropin induces SOCS-1 (suppressor of cytokine signaling-1) and SOCS-3 in FRTL-5 thyroid cells.
TSH has multiple physiological roles: it is required for growth, differentiation, and function of the thyroid gland, and it regulates transcription of interferon-gamma (IFN-gamma)-responsive genes in thyrocytes, including genes for the major histocompatibility complex and intercellular adhesion molecule-1. This report demonstrates that TSH induces the expression of suppressor of cytokine signaling (SOCS)-1 and -3 proteins and alters the phosphorylation state of signal transducer and activator of transcription (STAT) proteins STAT1 and STAT3. The expression of SOCS-1 and SOCS-3 and the phosphorylation state of STAT1 and STAT3 were examined after treatment with TSH or IFN-gamma in either TSH-sensitive FRTL-5 thyroid cells or TSH-insensitive FRT and buffalo rat liver (BRL) cells, which lack functional TSH receptors. SOCS-1 and SOCS-3 are constitutively expressed in FRTL-5 cells, but not in FRT and BRL cells. IFN-gamma up-regulated SOCS-1 and SOCS-3 RNA and protein in FRTL-5 cells, as reported previously for nonthyroid cells. Interestingly, TSH also significantly induced SOCS-1 and SOCS-3 in FRTL-5 cells, but not in FRT and BRL cells. When SOCS-1 or SOCS-3 was overexpressed in FRTL-5 cells, STAT1 phosphorylation at Y701 and STAT1/DNA complex formation in response to IFN-gamma were reduced. Furthermore, overexpression of either SOCS-1 or SOCS-3 significantly inhibited the IFN-gamma-mediated transactivation of the rat ICAM-1 (intercellular adhesion molecule-1) promoter. TSH and IFN-gamma had different effects on STAT1 and STAT3 phosphorylation. The phosphorylation of Y701 in STAT1, which is responsible for homodimer formation, nuclear translocation, and DNA binding, was specifically stimulated by IFN-gamma, but not by TSH or forskolin. However, the phosphorylation of S727 in STAT1 was induced by IFN-gamma, TSH, and forskolin. TSH induced phosphorylation of both Y705 and S727 in STAT3, while IFN-gamma phosphorylated only the Y705. In addition, we found that SOCS-3 was associated with JAK1 and JAK2 and that these associations were stimulated by TSH. These findings demonstrate that TSH induces SOCS in thyroid cells and provides the evidence of signal cross-talk between TSH and cytokines in thyroid cells.
Animals↗
Involvement of JAK/STAT (Janus kinase/signal transducer and activator of transcription) in the thyrotropin signaling pathway.
TSH is an important physiological regulator of growth and function in thyroid gland. The mechanism of action of TSH depends on interaction with its receptor coupled to heterotrimeric G proteins. We show here that TSH induces the phosphorylation of tyrosine in the intracellular kinases Janus kinase 1 (JAK1) and -2 (JAK2) in rat thyroid cells and in Chinese hamster ovary (CHO) cells transfected with human TSH receptor (TSHR). The JAK family substrates STAT3 (signal transducers and activators of transcription) are rapidly tyrosine phosphorylated in response to TSH. We also find that JAK1, JAK2, and STAT3 coprecipitate with the TSHR, indicating that the TSHR may be able to signal through the intracellular phosphorylation pathway used by the JAK-STAT cascade. TSH increases STAT3-mediated promoter activity and also induces endogenous SOCS-1 (suppressor of cytokine signaling-1) gene expression, a known target gene of STAT3. The expression of a dominant negative form of STAT3 completely inhibited TSH-mediated SOCS-1 expression. These findings suggest that the TSHR is able to signal through JAK/STAT3 pathways.
Animals↗
Development of a web-based picture archiving and communication system using satellite data communication.
Using the JAVA language we have developed a Web-based picture archiving and communication system (PACS) which allows a remote hospital to access medical images. An asymmetric satellite data communication system (ASDCS) provided a receive-only link for data delivery and a conventional terrestrial link (which could be the conventional telephone network) allowed data transmission. The satellite communication link was 10-30 times faster than the conventional terrestrial link. To increase image transmission speeds over the Internet connection, JPEG and wavelet compression methods were used. The resulting images were evaluated quantitatively by measuring the peak signal:noise ratio and qualitatively by radiologists. Compression ratios of 10:1 or less were deemed acceptable for diagnostic purposes. The system appears to be suitable for teleradiology and telemedicine.
Computer Communication Networks↗
Induction of osteopontin gene expression during mammary gland involution and effects of glucocorticoid on its expression in mammary epithelial cells.
To understand the molecular mechanisms of mammary gland involution, an involution-induced clone was identified from a cDNA library of mouse mammary gland by differential screening. Characterization of a clone by sequencing and northern analysis showed that expression of the osteopontin gene was induced during involution of mouse mammary gland. But induction of the osteopontin gene was not observed in apoptotic HC11 mammary epithelial cells under serum starvation. In HC11 cells, dexamethasone treatment from the seeding stage showed five-fold induction of osteopontin gene expression, but the expression was not changed when dexamethasone was added to confluent cells.
Animals↗
Differential response of obese gene expression from fasting in bovine adipose tissues.
To understand the molecular mechanism for intramuscular fat deposition, the expression of the obese gene was examined in response to fasting. Food deprivation for 48 h induced a decrease in the level of obese mRNA in pooled adipose tissues (abdominal, perirenal, subcutaneous, intermuscular and intramuscular). The expression of obese mRNA was examined for individual adipose tissue from several fat depots. It was highly expressed in perirenal adipose tissue, but fasting did not affect its expression level in this tissue. Moderate levels were detected in subcutaneous and intermuscular adipose tissues, and a fasting-induced decrease in obese mRNA was apparent in these tissues. The expression level of the obese gene in intramuscular adipose tissue was very low and did not respond to fasting.
Adipose Tissue↗
Bidirectional case-crossover studies of air pollution: bias from skewed and incomplete waves.
The case-crossover design compares exposures during the period of time of failure with one or more periods when failure did not occur and evaluates the potential excess risk using conditional logistic regression. In this simulation study, we applied several control sampling approaches to control for confounding by various temporal patterns of an exposure variable and evaluated the usefulness of symmetric bidirectional control strategies. We simulated true relative risks (RRs; true ss = 0.001) of deaths of 1.051 per 50-ppb increase of sulfur dioxide and included confounding by right- or left-skewed seasonal waves, linear long-term time trends, or a combination of both. The range of the estimated RRs from symmetric bidirectional control sampling approaches was 1.044 approximately 1. 056 at either a long-term trend or any skewed seasonal wave of SO(2) levels, which indicated the bidirectional control sampling methods would successfully control confounding by design. The simulations with bidirectional sampling, however, show that biases may occur if waves are incomplete (20-43% underestimated RRs). In conclusion, our simulations show that the symmetric bidirectional case-crossover design can substantially control for confounding by linear long-term trends and/or seasonality of an exposure variable by design as well. However, unidirectional control sampling would fail to control confounding by those variations of air pollution. Simulation results also show that even the bidirectional case-crossover design can be biased in a situation where the exposure variable shows incomplete cyclic waves, and therefore it cannot completely control for temporal confounding.
Air Pollution↗
Purification and embryotropic roles of tissue inhibitor of metalloproteinase-1 in development of "HanWoo" (Bos taurus coreanae) oocytes co-cultured with bovine oviduct epithelial cells.
This study was conducted to purify a tissue inhibitor of metalloproteinase (TIMP)-1 in a serum-free medium conditioned with bovine oviduct epithelial cells (BOEC) and to evaluate its effect on development of "HanWoo" (Bos taurus coreanae) embryos to the blastocyst stage. In the first study using SDS-PAGE electrophoresis, the presence of 32 kDa proteins, which contains TIMP-1, was detected in the medium conditioned with BOEC, and TIMP-1 was then purified from the medium by gel filtration and HPLC techniques. When examined TIMP-1 secretion, fluorescent foci indicating the secretion of TIMP-1 were found after stained BOEC with fluorescein isothiocyanate. In the next experiment, two-cell embryos derived from in vitro-fertilization were cultured in a serum-free medium, to which 0, 1.25, 2.5 or 5 microg/ml of purified TIMP-1 was supplemented. More (P<0.05) embryos developed to the morula and blastocyst stages after the addition of 2.5 microg/ml to culture medium than after no addition. In conclusion, our data indicate that BOEC secrete TIMP-1 and this glycoprotein promotes the prehatched development of "HanWoo" embryos derived from in vitro-fertilization.
Animals↗
Recent studies on natural products as anti-HIV agents.
The discovery of medicinal agents capable of specifically inhibiting human immunodeficiency virus (HIV) is urgently needed due to its globally widespread infection. Most of clinically useful anti-HIV agents are nucleosides but their use is limited due to their severe toxicity and emerging drug resistance. More than 50% of world marketed drugs have their origin of the nature. Natural products, of which structural diversity is so broad, are good sources for the effective discovery of anti-HIV agents with decreased toxicity. Over the past decade, substantial progress has been made in research on the natural products for the anti-HIV agents. New natural products that have potent anti-HIV activities with novel structures were reviewed in this article. These compounds, isolated mainly from medicinal plants, in this review have been classified as secondary metabolites such as terpenes, phenolics, and naturally scarce peptides and sugars. Especially, terpenes and phenol substances have gained much interest due to their significant anti-HIV activities along with their structural diversity. Recent studies also showed that several polysaccharides are effective inhibitors of HIV replication. Most of chemotherapeutic targets reviewed in this article are found to be HIV reverse transcriptase (RT).
Alkaloids↗
Zinc protoporphyrin IX concentrations between normal adults and the lead-exposed workers measured by HPLC, spectrofluorometer, and hematofluorometer.
To establish the relationship between Zinc protoporphyrin (ZPP) concentrations and blood lead (PbB) levels and to identify reliable analytical methods of ZPP and Protoporhyrin (PP), blood samples were obtained from 263 office workers without the history of occupational lead exposure and 49 lead-acid battery workers. The mean concentrations of PbB for the normal adults and the battery workers were 9.26 microg/dl and 42.60 microg/dl, respectively. The geometric mean concentrations of ZPP and PP by HPLC were 18.73 microg/dl and 2.27 microg/dl for normal adults and were 46.99 microg/dl and 5.53 microg/dl for the exposed workers, respectively. The geometric mean concentrations of ZPP and PP by a spectrofluorometer (SF) were 30.27 microg/dl and 5.16 microg/dl for normal adults and were 50.91 microg/dl and 6.69 +/- 1.39 microg/dl for the exposed workers. The geometric mean ZPP concentration measured by a hematofluorometer (HF) was 30.88 microg/dl for normal adults. The results showed that ZPP concentrations measured by HF were consistently higher than those by HPLC and SF for normal adults, and lower for the exposed workers. ZPP concentrations were not correlated with PbB levels for normal adults but a statistically significant correlation was found among the exposed workers.
Adult↗
Aminoguanidine-induced amelioration of autoimmune encephalomyelitis is mediated by reduced expression of inducible nitric oxide synthase in the spinal cord.
To elucidate whether an inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (AMG), affects the expression of iNOS in the spinal cords of rats with experimental autoimmune encephalomyelitis (EAE), we induced EAE in Lewis rats, and treated EAE rats with AMG. AMG (200mg/kg administered intraperitoneally from day 0 to day 7 post-immunization) significantly reduced the clinical severity of EAE paralysis. AMG, however did not prevent the occurrence of EAE. Western blot analysis showed that iNOS expression was significantly reduced in the spinal cords of rats with EAE treated with AMG compared with rats treated with the vehicle. This finding supports the conclusion that the production of nitric oxide by iNOS plays an important role in the induction of EAE. The corollary is that the amelioration of EAE paralysis by the treatment with AMG is associated with the suppression of iNOS expression in the target organ i.e. the spinal cord.
Animals↗