AN APPROXIMATE CELL MODEL FOR LIQUID HYDROGEN, I.
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Journal Article↗
Biomedical subjects
S Kim
Publications and source records attributed to S Kim.
Reconstitution of a metabolic pathway with triple-cistronic IRES-containing retroviral vectors for correction of tetrahydrobiopterin deficiency.
BACKGROUND: Tetrahydrobiopterin (BH4) is an essential cofactor for catecholamine and serotonin neurotransmitter biosynthesis. BH4 biosynthesis is carried out in a three-enzyme pathway involving GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase (PTPS) and sepiapterin reductase (SR). Treatment of genetic defects leading to BH4 deficiency requires neurotransmitter replacement since synthetic cofactor does not efficiently penetrate the blood-brain barrier. Autologous fibroblasts transplanted into the brain as depository cells for drug delivery might offer an alternative. However, normal fibroblasts do not express GTPCH, and fibroblasts from PTPS patients lack two biosynthetic enzymes for BH4 production. METHODS: We engineered primary fibroblasts by the use of triple-cistronic, retroviral vectors for cofactor production. RESULTS: Constitutive SR activity in these cells enabled BH4 biosynthesis by transducing GTPCH and PTPS cDNAs together with a selective marker coupled in a single transcript with two IRES-elements in tandem. Upon reaching a critical concentration (> 400 pmol/mg protein) of intracellular BH4, the fibroblasts efficiently released cofactor even under non-dividing conditions. CONCLUSION: The use of triple-cistronic vectors for single transduction to reconstitute metabolic pathways or to treat multi-genetic diseases may be useful for engineering, for instance, depository cells for various organs, including the nervous system.
Biopterins↗
Enzymatic modification of nuclear proteins during neoplastic growth.
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Acetylation↗
Suprageneric classification of peptidoglycan group B actinomycetes by nucleotide sequencing of 5S ribosomal RNA.
5S ribosomal RNA sequences were determined for thirteen actinomycetes mainly representatives with the rare group B type peptidoglycan. The primary and secondary structure of the resultant sequences were of the type characteristic of Gram-positive bacteria with DNA rich in guanine plus cytosine. The sequencing and associated chemotaxonomic data provide compelling grounds for classifying actinomycetes with a group B type peptidoglycan in a single family. The family Microbacteriaceae fam. nov. is proposed to accommodate actinomycetes classified in the genera Agromyces, Aureobacterium, Clavibacter, Curtobacterium and Microbacterium.
Actinomyces↗
Prevalence of human foamy virus-related sequences in the Korean population.
The possible association of human foamy virus (HFV) with human thyroid disorders such as Graves' disease (GD) has been a topic of controversy due to the inconsistent results reported by several groups of investigators. Here we report the investigation of the presence of HFV-related sequences in the Korean population. DNA was obtained from peripheral blood lymphocytes from 24 GD patients and 23 healthy blood donors and subjected to PCR amplification using three sets of nested primers derived from gag, env, and LTR regions of the HFV genome. Contrary to previously reported studies, our analysis identified HFV-related sequences in the genomes of both healthy individuals and the GD patients. However, the nature of the HFV genome present in each group appeared to be different. We detected all 3 regions of HFV-related sequences in 29% of the HFV-positive GD patients, while no samples in the control group amplified all three regions. This suggests that the LTR may be used as a tool for screening for HFV in GD patients. Our data favor the hypothesis of a relationship between GD and the presence of HFV-related sequences, though in a complex way.
Adult↗
Is lymphadenectomy necessary for early gastric cancer?
BACKGROUND: Although early gastric cancer (T1, NX) in Japan has been reported to have an excellent prognosis, the experience with this cancer in the United States is limited. The treatment of these tumors in Japan is becoming less aggressive as "good prognostic factors" are increasingly recognized. Our objective was to identify predictors of nodal disease and survival in a large cohort of Western patients with T1 tumors. METHODS: A retrospective review of our prospective data base from July 1985 to March 1998 revealed 165 patients undergoing surgical resection for T1 gastric tumors. Clinicopathological factors analyzed and compared included presence of positive nodes, tumor size (> or =4.5 vs. <4.5 cm), depth (mucosal vs. submucosal), grade (poor vs. moderate and well), and tumor site (proximal vs. distal), presence of venous or perineural invasion, and Lauren's classification. Factors predicting lymph node involvement and disease-specific survival were evaluated by univariate and multivariate analysis. RESULTS: Median follow-up time was 36 months. The actuarial 5-year survival was 88%. Thirteen patients (8%) died of disease. Lymph node involvement was present in 31 tumors (19%), with a 5-year survival of 91% with negative nodes vs. 78% with positive nodes. On univariate and multivariate analysis, the presence of tumor submucosal invasion (P<.05), venous invasion (P = .02), and size of 4.5 cm and larger (P = .02) was significantly associated with an increased risk for nodal positivity. On univariate analysis of survival, node-positive tumors (P = .02) and tumors 4.5 cm and larger (P = .008) were significantly associated with decreased survival. On multivariate analysis, only node-positive tumors were significantly (P = .01) associated with decreased survival. Those tumors that were limited to the mucosa and less than 4.5 cm in size (n = 47) had a 4% rate of positive nodes. In contrast, those tumors that were 4.5 cm and larger and had penetrated into the submucosa (n = 16) had a 56% chance of positive nodes. CONCLUSIONS: Early gastric carcinoma in North America has an excellent prognosis, similar to that in Japan. Tumors that are limited to the mucosa and smaller than 4.5 cm could be considered for limited resection without lymphadenectomy.
Adult↗
[Des-Met14]bombesin analogues function as small cell lung cancer bombesin receptor antagonists.
A series of bombesin (BN) analogues lacking the C-terminal methionine at the 14 position were evaluated as BN receptor antagonists. [D-Phe6]BN(6-13)amide inhibited specific 125I-GRP binding to lung cancer cell line NCI-H720 with an IC50 value of 12 nM. In contrast, [D-Phe6]BN(6-13)propylamide, butylamide and methylester were more potent with IC50 values of 3, 5 and 5 nM whereas [D-Phe6,Sta13]BN(6-13)amide was less potent with an IC50 value of 180 nM. [D-Phe6]BN(6-13)propylamide antagonized the ability of BN to elevate cytosolic Ca2+, whereas [D-Phe6]BN(6-13)butylamide was a partial agonist. In a small cell lung cancer (SCLC) growth assay, [D-Phe6]BN(6-13)propylamide inhibited colony formation. In summary, BN analogues which lack a C-terminal methionine may function as useful SCLC BN receptor antagonists.
Bombesin↗
Antagonistic effect of D-myo-inositol-1,2,6-trisphosphate (PP56) on neuropeptide Y-induced vasoconstriction in the feline dental pulp.
Intra-arterial injection of neuropeptide Y (NPY) (1.3-2.0 micrograms/kg) resulted in decreases of pulpal blood flow by 37.7 +/- 5.7% (mean +/- SEM). The intra-arterial injection of D-myo-inositol-1,2,6-trisphosphate (PP56) (0.3 mg/kg) alone changed pulpal blood flow by 1.0%. The effect of NPY in the presence of PP56 resulted in significantly smaller decreases in pulpal blood flow ranging from 27.2 +/- 5.4 to 16.6 +/- 3.5% from control as compared with NPY alone. In effect, PP56 partially blocked the decreases in pulpal blood flow caused by NPY. The electrical stimulation of the sympathetic nerve alone resulted in decreases in pulpal blood flow of 41.7 +/- 6.2%. The electrical stimulation of the sympathetic nerve following the intra-arterial administration of PP56 decreased pulpal blood flow by 23.1 +/- 6.0% from control, significantly less than the sympathetic nerve stimulation alone. PP56 attenuated the decrease in pulpal blood flow caused by the sympathetic nerve stimulation by 44.4 +/- 11.0%. Similarly, the combination of PP56 and phentolamine followed by electrical stimulation of the sympathetic nerve reduced the decrease in pulpal blood flow caused by the sympathetic nerve stimulation alone by 43.0 +/- 8.6%. These results provide evidence that the non-peptide PP56 is capable of antagonizing vasoconstriction caused by NPY in the feline dental pulp. In addition, they show functional evidence that NPY as well as noradrenaline are released from the sympathetic nerve endings during its stimulation and cause vasoconstriction.
Animals↗
Oxidant stress and antioxidant capacity in urine of renal transplant recipients predict early graft function.
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Biomarkers↗
Induction of B cell proliferation and NF-kappa B activation by a water soluble glycan from Lentinus lepideus.
Many immune modulating compounds have been isolated from fungal extracts, but the molecular mechanisms of their action have rarely been elucidated. In this study we isolated a proteoglycan from cultured mycelia of Lentinus lepideus and tested its effects on murine spleen cells. The acidic-polysaccharide fraction was obtained by extraction with hot water followed by purification using DEAE-cellulose anion exchange. The molecular mass of the compound was determined by Sepharose CL-4B gel filtration to be approximately 47 kDa. When cultured in the presence of the compound, spleen cells from C3H mice underwent rapid cell proliferation and cell aggregation. Treatment with the compound also caused a 10-fold increase in [3H]-thymidine incorporation compared to a control, confirming cell proliferation. Flow cytometry analysis indicated that the affected cell population was mainly B cells. As one approach to understanding the molecular mechanism of this action, we investigated the effects of the compound on cellular transcription factors which are known to control the proliferation of immune cells. Using gel retardation assays, we found that the compound significantly activated NF-kappa B but not AP-1 in spleen cells. Taken together, the data suggest that the proteoglycan compound is a biological response modifier that stimulates B cell proliferation, probably by regulating cellular transcription factors such as NF-kappa B.
Animals↗
Distribution of blood flow in an experimental palatal carcinoma.
Tumor perfusion is an important factor in the success of many common and potential therapeutic and diagnostic modalities. We studied blood flow of an experimental squamous cell carcinoma of the rat palate using the radionuclide-labeled microsphere injection method. Tumors (N = 14) were studied for level and distribution of blood flow, and changes in blood flow with increasing size. The results show a wide variation in the absolute level of perfusion among the tumors, but a consistent pattern of blood flow distribution, with poor perfusion in the central parts and a sharp increase in perfusion at the periphery. The blood flow (in mL/min/100 g) in the five zones from center to periphery were 2.32 +/- 5.7, 5.62 +/- 16.3, 4.20 +/- 6.87, 15.04 +/- 23.6, and 32.31 +/- 41.8. The average level of perfusion decreased as tumor size increased, but the pattern of blood flow distribution remained constant. The data from this study provide an understanding of the basic pattern of blood flow in an experimental squamous cell carcinoma of the head and neck, and will serve as a foundation to further explore the hemodynamic characteristics of head and neck carcinomas.
Animals↗
Prediction of optimal injection protocol for tumor detection in contrast-enhanced dynamic hepatic CT using simulation of lesion-to-liver contrast difference.
The detection of hepatic lesions in computed tomography (CT) is improved when a contrasting material is administered intravenously, but it depends considerably on how this agent is injected. In this study, we constructed a compartment model for a liver containing a hepato-cellular carcinoma (HCC), and simulated the difference in lesion-to-liver contrast enhancement. Using this model, we simulated the effects of various injection factors on the detectability of a lesion and searched for the optimal injection protocol for detecting tumors in contrast-enhanced dynamic hepatic CTs. We found that the mass injection rate, or k-value (in mg/s), (which is the volume injection rate, in ml/s, multiplied by the contrast agent concentration, in mg/ml) plays a critical role in the injection protocol optimized for tumor detection, and has a unique value for a given body weight independent of the total injection dose.
Adult↗
Drainage efficiency of double-lumen sump catheters and single-lumen catheters: an in vitro comparison.
PURPOSE: To compare the drainage efficiency of double-lumen sump catheters and single-lumen catheters in an in vitro model. MATERIALS AND METHODS: Four 12-F, 27.5-cm catheters were used in the study. Three of these had a double lumen with a 7-F internal diameter drainage lumen and one had a single lumen with an 8-F internal diameter drainage lumen. The sump hole opened internally to the drainage lumen in one catheter, opened externally in one catheter, and was occluded in one catheter. Catheters were connected to continuous low-wall suction and were immersed in water, viscous fluid, and viscous fluid with particles. The volume of fluid drained by each catheter was measured and compared. RESULTS: The single-lumen catheter with an 8-F internal diameter drainage lumen drained a volume equal to or larger than that for double-lumen catheters with a 7-F internal diameter drainage lumen for each type of fluid. The open sump of the double-lumen catheters may have decreased the catheter's drainage efficiency by allowing air to be suctioned into the catheter. CONCLUSION: Single-lumen catheters performed as well as or more efficiently than double-lumen catheters of the same outer diameter in this in vitro model.
Catheterization↗
Analysis of 154 actual five-year survivors of gastric cancer.
Gastric cancer patients in the United States have a poor prognosis with a collective 5-year survival rate of less than 15%. We identified a subset of actual 5-year survivors (long-term survivors) and analyzed clinicopathologic variables predictive of recurrence and survival beyond the 5-year mark. A review of our prospective database from July 1985 to February 1993 revealed 154 patients who were long-term survivors and 280 patients who died of disease prior to 5 years (short-term survivors) following curative resection (R0). Tumor (T) stage, nodal (N) status, tumor location, and median number of positive nodes were compared between the two groups. Univariate and multivariate analysis of disease-free and greater than 5-year disease-specific survival was performed within the long-term survivors. Among the long-term survivors, 29% were classified as "early gastric cancers" (T1NX). The median number of positive nodes (0 vs. 5; P <0.001) and percentage of lesions that were T1/T2 (60% vs. 19%; P <0.001), node negative (58% vs. 15%; P <0.001), or proximal (40% vs. 65%; P <0.001) was significantly different in long-term survivors vs. short-term survivors, respectively. Of the 154 five-year survivors, gastric cancer recurred in 23, and 13 patients (8%) died of the disease at a median of 84 months from the original diagnosis. On univariate and multivariate analysis of prognostic factors in the long-term survivors, only the Lauren histologic classification predicted disease-specific and disease-free survival with diffuse histologic types faring significantly less well. T stage and N status are powerful prognostic factors of outcome within the first 5 years after curative resection of gastric carcinoma. However, the Lauren histologic type emerges as the dominant predictor of outcome once a patient with gastric cancer has survived for 5 years or more.
Female↗
Ectopic expression of reg protein: A marker of colorectal mucosa at risk for neoplasia.
Pancreatic regenerating gene (reg I) messenger RNA is overexpressed within the pancreas following injury and resection. Its level of expression corresponds to the level of cellular dedifferentiation. Human reg I has been localized to chromosome 2p12, and ectopic expression of its mRNA has been found within colorectal tumors. We postulated that colorectal production of reg I might either be a marker for the presence of cancer or define mucosa at risk for development of neoplasia. Using a monoclonal antibody to reg I, regenerating gene protein was histochemically mapped in 56 cases of documented colorectal adenocarcinoma. In sections of colon from normal control subjects no reg I protein was noted, whereas 58.9% of the specimens from cancer patients stained positive for reg I. Although a correlation was noted between reg I staining and Dukes' stage, there was no correlation with histologic grade or 5-year patient survival. In 39 of 55 cancer specimens the transition zone (interface) between the neoplasm and normal mucosa was visualized; 100% of the transition zones contained cells that stained strongly positive for reg I. We conclude that reg I protein is ectopically expressed in colorectal mucosa at the transition zone of colorectal cancer, and occasionally within the tumor itself. Although ectopic reg I expression in colorectal epithelia is not a marker for the presence of carcinoma, it may be a sensitive marker for mucosa at risk for development of neoplasia.
Adenocarcinoma↗
Effects of glycerol of beta-lactamase production during high cell density cultivation of recombinant Escherichia coli.
Recombinant Escherichia coli was cultured up to OD600 90 with glycerol fed by the DO-STAT method to produce recombinant beta-lactamase. Optimum feeding and induction conditions were determined. When glycerol was maintained at a high concentration (40-50 g/L) after isopropyl thiogalactoside (IPTG) induction at OD600 75, a 2-fold increase in the amount of soluble beta-lactamase was obtained. Similarly, a 3-fold increase was obtained by the addition of NaCl (0.4 M) at low glycerol concentration (10 g/L).
Escherichia coli↗
Formation and stability of pyrrole adducts in the reaction of levuglandin E2 with proteins.
Levuglandin (LG) E2 is rapidly sequestered by covalent binding with proteins. The reaction of LGE2 with a protein in neutral aqueous solution exhibits two phases. A metastable adduct rapidly accumulates initially. In the second phase, a protein-bound pyrrole is generated. Pyrrole formation and stability were monitored with an immunoassay using antibodies that were raised against a stable isostere. That LG-derived pyrroles are the major products (> 76%) of the LGE2-protein reaction is suggested by the level of antibody binding found for LG-protein adducts compared with that found for a pyrrole derived from LGE2 and 6-amino-1-hexanol. Because the initial metastable LG-protein adduct is a reactive electrophile, it can be trapped with amines, such as glycine, to give stable ternary adducts that do not cross-react with the antibodies. Although highly alkylated pyrroles are chemically sensitive compounds, the protein-bound LG-derived pyrrole appears to be stable in aqueous solution at pH 7.4. Thus, it shows no decrease in immunoreactivity over several weeks. This discovery leads to the expectation that such pyrroles will accumulate in vivo, especially in proteins that do not turn over rapidly. Thus, the LG-derived protein-bound pyrrole may be a useful marker of oxidative lipid damage, and an immunoassay for this post-translational protein modification can be exploited as a mild, sensitive method for detecting and quantifying the generation of LGs in chronic inflammatory states.
Animals↗
Effects of high-fat diet, angiotensinogen (agt) gene inactivation, and targeted expression to adipose tissue on lipid metabolism and renal gene expression.
To address the role of angiotensinogen (agt) in lipid metabolism and its potential endocrine effects in vivo, we studied the effects of high-fat diet (HFD) on adult, 28-week-old agt knockout (KO) mice compared to wild type (WT) mice. Recent studies (Massiera et al., 2001) have demonstrated that reexpression of agt in adipose tissue of KO mice normalized adiposity, blood pressure, and kidney abnormalities. We therefore used microarray analysis to investigate changes in gene expression profile in kidneys of KO vs. Tg-KO mice, where agt expression is restricted to adipose tissue. Body weight, adiposity and insulin levels were significantly decreased (p < 0.05) in KO mice on a chow diet (CD) compared to WT mice, while circulating leptin levels were similar. On a high-fat diet, KO mice exhibited significantly lower bodyweight (p < 0.05), adiposity (p < 0.05), leptin, and insulin levels (p < 0.05) compared to WT mice. In agreement with previously reported changes in kidney histology, agt KO mice displayed altered expressions of genes involved in blood pressure regulation and renal function, but these levels were corrected by reexpression of agt in adipose tissue. Collectively, these findings further document important endocrine roles of adipocyte agt, in part via regulation of lipid metabolism and kidney homeostasis.
Adipose Tissue↗