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Biomedical subjects

C Wu

Publications and source records attributed to C Wu.

610 records · Page 34Linked to original sources
PubMedDate not supplied

Effect of ethanol on ascorbate release in the nucleus accumbens and striatum of freely moving rats.

An in vivo voltammetry technique was used to monitor the extracellular ascorbate (AA) concentration in the nucleus accumbens and striatum of unanesthetized, freely moving rats. A single injection of ethanol, 1.0 g/kg intraperitoneally (IP), induced a significant increase in extracellular AA concentration in both the nucleus accumbens and striatum. This effect was dose dependent within a dose range from 0.5-2.0 g/kg. 4-Methylpyrazole (50 mg/kg, IP), which inhibits alcoholdehydrogenase, could not prevent the increase in AA concentration, evoked by ethanol. Furthermore, systemic administration of acetaldehyde (20 mg/kg, IP), the main metabolite of ethanol, did not have any effect on the level of AA in the nucleus accumbens or striatum. These results show that ethanol can alter the brain extracellular AA levels and that this effect seems to be attributed to ethanol itself and not to acetaldehyde. Consequently, these results indicate that a role for AA in the action of ethanol in the brain should be considered.

Animals↗
PubMedDate not supplied

Determination of the adsorption of tramadol hydrochloride by activated charcoal in vitro and in vivo.

Although tramadol is one of the most widely used centrally acting analgesics worldwide, no literature is available regarding adsorption of tramadol HCl powder or tablets (Ultram; 50 mg tramadol HCl per tablet) by activated charcoal (AC) for use as potential adjunct treatment of overdose. The present study incorporated a novel combination of in vitro and in vivo methods to investigate this question. Based on a binding curve of tramadol UV absorbance (UV(a); 225 nm) plotted against the amount of AC, the ratio of amount of tramadol completely adsorbed by AC was 0.05 mg/mg. Also based on UV(a), no tramadol was detected in filtrate of slurries in which up to 62 tablets of Ultram were mixed with 50 g AC; 4.6% of unbound tramadol was detected when 100 tablets of Ultram were mixed with AC. The ratio of amount of tramadol completely adsorbed by AC in this test was 0.10. In vivo, co-administration of 0.1 g/ml of AC produced a 13- to 14-fold rightward shift in tramadol's antinociceptive dose-response curve and a 1.6-fold rightward shift in tramadol's lethality dose-response curve.

Adsorption↗
PubMedDate not supplied

Influence of lumbar spine pathology on the incidence of paresthesia during spinal anesthesia.

BACKGROUND AND OBJECTIVES: Paresthesia occasionally occurs during dural puncture or injection of local anesthetic for spinal anesthesia. Although the incidence of neurologic complications after spinal anesthesia is extremely low, the significance of paresthesia is unknown. The influence of known lumbar spine pathology on the incidence of paresthesia during spinal anesthesia is studied. METHODS: Incidence of paresthesia with dural puncture (PP) or injection (PI) was studied in two groups of patients. Group 1 included patients for elective total joint replacement without known spine pathology or complaints. Group 2 included patients for elective lumbar spine surgery who received spinal anesthesia. RESULTS: Significantly more PP (20% vs 9%) and PI (16% vs 6%) occurred in the spine surgery group. There were no neurologic sequelae of spinal anesthesia. CONCLUSIONS: This information suggests that the incidence of paresthesia during the conduct of spinal anesthesia is higher in patients with lumbar spine pathology. Although there were no neurologic complications, the sample size is too small to exclude an increase in the neurologic risk of spinal anesthesia in patients with known intraspinal pathology.

Adrenergic Agonists↗
PubMedDate not supplied

Synthesis of 2-(p-thiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid: application of the 4-methoxy-2,3,6-trimethylbenzenesulfonamide protecting group in the synthesis of macrocyclic polyamines.

A synthesis of the bifunctional chelator 2-(p-thiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid [2-(p-NCS-Bz)-NOTA] is described which illustrates the especial utility of the (4-methoxy-2,3,6-trimethylphenyl)sulfonyl (Mtr) protecting group as an alternative to the p-tolylsulfonyl (Ts) moiety commonly used for Richman-Atkins type cyclizations. Reaction of N,N'-bis(p-tolylsulfonyl)-1-(p-benzamidobenzyl)ethylenediami ne with N,N-bis[2-[(p-tolylsulfonyl)oxy]ethyl]-p-toluenesulfonamide gave 2-(p-benzamidobenzyl)-1,4,7-tris(p-tolylsulfonyl)-1,4,7-tria zacyclononane in 55% yield, whereas the analogous reaction using the Mtr-protected starting materials gave the corresponding Mtr-protected macrocycle in 34% yield. However, deprotection of the Ts- and Mtr-protected macrocycles (H2SO4, 90 degrees C) afforded 2-(p-benzamidobenzyl)-1,4,7-triazacyclononane in 23% and 60% yield, respectively, illustrating the relatively facile cleavage of the Mtr moiety. A modest improvement in overall percent conversion of (p-nitrobenzyl)ethylenediamine into substituted macrocyclic polyamine was observed when comparing the Mtr vs Ts protection (12.6 vs 10.6%). The macrocyclic triamine was converted to 2-(p-NCS-Bz)-NOTA by alkylation with bromoacetic acid (pH 9, 73%) followed by hydrolysis of the benzamide protecting group (6 M HCl, 70 degrees C, 87%) and reaction with thiophosgene (90%). The serum stability of the 67Cu complexes of 1,4,7-triazacyclononane (I), 2-(p-nitrobenzyl)-1,4,7,10-tetraazacy-clododecane (II), 2-(p-nitrobenzyl)-1,4,8,11-tetraazacyclotetradecane (III), 2-(p-PhCONH-Bz)-NOTA (IV), 2-(p-nitrobenzyl)-1,4,7,10-tetraazadodecane-1,4,7,10-tetraacetic acid (V), 2-(p-nitrobenzyl)-1,4,8,11-tetraazatetradecane-1,4,8,11-tetraaceti c acid (VI), and the acyclic ligand 1-(p-nitrobenzyl)-4-methyldiethylenetriamine-N,N,N',N", N"-pentaacetic acid (VII) was measured at 37 degrees C (5% CO2) and showed the following order of relative stability: I < VII << VI << IV < V approximately equal to II approximately equal to III.

Animals↗
PubMedDate not supplied

Biodistribution and catabolism of Ga-67-labeled anti-Tac dsFv fragment.

The disulfide-linked fragment (dsFv) of the antibody to the alpha subunit of the IL2 receptor has been radiolabeled with a [Ga-67] Ga-2-(p-SCN-Bz)-NOTA derivative linked through an isothiocyanato group to either the epsilon-amino group of lysine or the alpha-amino group of the N-terminal amino acids. This low molecular weight protein (LMWP) has been proposed as a tumor diagnostic agent. However, > 60% of the injected dose localized in the mouse kidney. The major catabolites (> 95%) in the kidney were identified as the Ga-2-(p-SCN-Bz)-NOTA conjugate with either lysine or methionine, with no evidence of transchelation of Ga-67. Since different amino acids in the dsFv were radiolabeled according to this procedure, it was possible to study the relative residence times of the various catabolites. The methionine conjugate had a significantly shorter residence time than the lysine conjugate in the same kidney. Labeling the appropriate amino acid in a LMWP may lead to reduced residence times and increased diagnostic or therapeutic ratios.

Animals↗
PubMedDate not supplied

Evaluation of the in vivo biodistribution of indium-111 and yttrium-88 labeled dendrimer-1B4M-DTPA and its conjugation with anti-Tac monoclonal antibody.

We evaluated the in vivo biodistribution of indium- and yttrium-labeled second-generation polyamidoamine dendrimer (PAMAM) conjugated with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M), a derivative of DTPA. In addition, we conjugated PAMAM-1B4M to humanized anti-Tac IgG (HuTac) and evaluated its in vitro and in vivo properties. PAMAM-1B4M was labeled with 111In at 37-48 MBq/mg (1.0-1.3 mCi/mg) or with 88Y at 3.7-4.8 MBq/mg (0.1-0. 13 mCi/mg), and an aliquot of radiolabeled conjugate was saturated with the corresponding stable yttrium or indium. Nontumor-bearing nude mice were injected intravenously with 55.5-66.6 kBq (1.5-1.8 microCi) of 88Y-labeled PAMAM-1B4M or with 185 kBq (5 microCi) of 111In-labeled PAMAM-1B4M. The mice were then sacrificed at 15 min, 90 min, 1 day, and 4 days postinjection. Then the PAMAM-1B4M was conjugated with HuTac and labeled with 111In at 111-259 MBq/mg (3-7 mCi/mg). Another preparation of 111In-labeled HuTac-PAMAM-1B4M was saturated with stable indium. Immunoreactivity of both preparations and biodistribution in normal mice 1 h after injection and in ATAC4 and A431 tumor-bearing mice 18 h after injection were evaluated and compared with those of 111In-labeled 1B4M-HuTac. We noted significantly higher accumulations (p < 0.05) of 111In-labeled and 88Y-labeled unsaturated PAMAM-1B4M than saturated preparations in the liver, kidney, spleen, and bone at most time points. The whole-body clearance times of unsaturated preparations were significantly slower than those of saturated preparations at all time points, with the exception of 168 h for 111In-labeled PAMAM-1B4M. The saturated preparation of 111In-labeled HuTac-PAMAM-1B4M showed lower hepatic uptake (27 +/- 2%ID/g) than the unsaturated (32 +/- 2%ID/g), but greater than the HuTac-1B4M control (10 +/- 0%ID/g). The splenic uptake showed 15 +/- 1, 38 +/- 5, and 8 +/- 1%ID/g for the saturated, unsaturated, and control, respectively. The biodistribution of the dendrimer conjugated HuTac in normal organs of tumor-bearing mice was similar to nontumor-bearing mice. Specific tumor (ATAC4) uptake was higher than that in nonspecific tumor (A431). In conclusion, we evaluated the biodistribution of radiolabeled PAMAM-1B4M. We noted high accumulation in the liver, kidney, and spleen, which significantly decreased when the chelates were saturated with the stable element. A similar phenomenon was observed between unsaturated and saturated 111In-labeled HuTac-PAMAM-1B4M, indicating that the PAMAM dendrimer had a detrimental effect on biodistribution.

Animals↗
PubMedDate not supplied

Activating protein factor binds in vitro to upstream control sequences in heat shock gene chromatin.

DNA sequences, important for the control of Drosophila heat shock gene expression, are packaged in chromatin in a nuclease hypersensitive configuration. Recently, two protein-binding (exonuclease-resistant) sites which cover the TATA box sequence and an upstream control element were shown to occur in vivo amidst the 5' terminal hypersensitive regions of several heat shock genes. Protein-binding at the TATA box is independent of heat shock, but the binding at the upstream element is heat shock dependent, and it was proposed that a heat shock activator protein, HAP, positively regulates the genes. Here, I report the detection of HAP activity in heat shocked cell extracts by reconstituting specific binding to hsp82 gene chromatin in vitro. Inhibition of the binding by free DNA from the 5' region of heat shock genes implies a coordinate regulation of the gene family through HAP interaction with the upstream heat shock consensus sequence. Furthermore, the special ease of induction of the hsp82 gene over other heat shock genes can be explained in molecular terms by the higher affinity of HAP for the hsp82 binding site, which contains a 28 base sequence with almost perfect dyad symmetry, GAAGCCTCTAGAAG/TTTCTAGAGACTTC.

Animals↗
PubMedDate not supplied

An exonuclease protection assay reveals heat-shock element and TATA box DNA-binding proteins in crude nuclear extracts.

The ability to identify and purify trans-acting cellular factors that regulate eukaryotic genes is limited by the lack of a practical general assay. Current procedures using crude whole cell or nuclear extracts that restore transcriptional function in vitro or permit reconstruction of native chromatin at control sequences are effective only in select systems. I now present an exonuclease protection assay that is generally applicable for detecting sequence-specific DNA-binding proteins. The assay extends earlier work on the binding to the Drosophila heat-shock gene control element of a protein factor (HAP) present in crude nuclear extracts; the binding was shown by reconstitution of specific exonuclease resistance within a nuclease-hypersensitive site in chromatin. We show here that this same exonuclease resistance can be reconstituted on free linear DNA, despite many nonspecific binding activities present in unfractionated nuclear extracts. We have further applied this assay method to fractionate the protein factor that is bound constitutively to the heat-shock gene TATA box region in native chromatin. Exonuclease protection offers a sensitive, precise and rapid assay for any sequence-specific DNA-binding protein.

Animals↗
PubMedDate not supplied

Induction of sequence-specific binding of Drosophila heat shock activator protein without protein synthesis.

Drosophila tissue culture cells stimulated by heat shock contain high levels of heat shock activator protein, which binds specifically to the heat-shock control DNA element. In contrast, nonshocked cells have low basal levels of binding activity. Here, we show that within 30 seconds of heat shock of intact cells the sequence-specific binding activity in whole cell extracts increases significantly, reaching a plateau by 5 min after the start of the shock; removal of the heat stimulus returns the activity to basal levels. Known chemical inducers of heat-shock genes elicit a similar pattern of specific binding activity. Moreover, this pattern is observed in the presence of protein synthesis inhibitors, even if the stimulus-withdrawal is repeated sequentially through five cycles. Our results are inconsistent with models which propose proteolysis as the chief means of mediating heat-shock transcriptional control. Rather, they suggest that heat shock activator pre-exists in normal cells in a nonbinding form, which is converted upon cell stimulus to a high affinity, sequence-specific binding form, most probably by a post-translational modification. This conversion may be crucial for the transcriptional activation of heat shock genes.

Animals↗
PubMedDate not supplied

Efficacy of chlorine dioxide as a gas and in solution in the inactivation of two trichothecene mycotoxins.

The efficacy of chlorine dioxide (ClO2) in detoxifying two potential bioterrorism agents, the trichothecene mycotoxins verrucarin A and roridin A, was evaluated. In the first experiment, verrucarin A (1, 5, or 10 microg) and roridin A (5 or 10 microg) were each inoculated onto square-inch sections of glass, paper, and cloth and exposed to 1000 ppm of ClO2 for either 24 or 72 h at room temperature. In the second experiment, verrucarin A and roridin A (1 or 2 ppm in water) were treated with 200, 500, or 1000 ppm ClO2 for up to 116 h at room temperature in light and dark conditions (N = 9 per treatment for test and control). A yeast assay using Kluyveromyces marxianuswas used to quantify the toxicity of verrucarin A and roridin A. Additionally, high-performance liquid chromatography was performed on selected samples. Results for the first experiment showed that ClO2 treatment had no detectable effect on either toxin. For the second experiment, both toxins were completely inactivated at all tested concentrations in as little as 2 h after treatment with 1000 ppm ClO2. For verrucarin A, an effect was seen at the 500 ppm level, but this effect was not as strong as that observed at the 1000 ppm level. Roridin A toxicity was decreased after treatment with 200 and 500 ppm ClO2, but this was not significant until the 24-h exposure time was reached. These data show that ClO2 (in solution) can be effective for detoxification of roridin A or verrucarin A at selected concentrations and exposure times.

Bioterrorism↗
PubMedDate not supplied

Collagenase and protease activities in head and neck tumors.

An analysis of specimens of 43 head and neck tumors revealed that collagenase and protease activities paralleled each other and varied according to the anatomic site; highest activities were in tongues and tonsils, which are known to have low five-year survival rates. The greatest differences in both enzyme activities were observed in the studies of histologic patterns and tumor differentiation. The ulcerated tumors with inflammatory infiltrates having high enzyme activities suggest that collagenase and protease may be derived from inflammatory cells.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

A new cell proliferating marker: cytosolic thymidine kinase as compared to proliferating cell nuclear antigen in patients with colorectal carcinoma.

BACKGROUND: Proliferation markers are necessary for reliable diagnosis. Here we have presented for the first time thymidine kinase 1 (TK1) as a proliferative tumor marker for colorectal carcinoma. PATIENTS AND METHODS: Expression of TK1 in 54 colorectal lesions and 20 colorectal adenoma lesions was detected by immunohistochemistry technique (ABC). Proliferating Cell Nuclear Antigen (PCNA) was run in parallel. RESULTS: TK1-Labelling Index (LI) (65%) was higher than PCNA-LI (52%) in the malignant lesions, although not significantly different (p = 0.1717) between them. TK1-LI as well as PCNA-LI showed significant differences between colorectal carcinoma and colorectal adenoma (TK1 p = 0.0005, PCNA p = 0.0005). Both TK1-LI and PCNA were significantly different in respect to tumor stages (TK1 p = 0.0002, PCNA p = 0.0284). However, only TK1-LI showed significant difference in respect to tumor grades (p = 0.014), but not PCNA-LI (p = 0.132). CONCLUSION: TK1-LI showed more potential as a proliferating marker in colorectal carcinoma than PCNA-LI, especially for evaluating high-risk tumor grade and advanced stage in colorectal carcinoma.

Adenocarcinoma, Papillary↗
PubMedDate not supplied

Spontaneous abortion rate in patients with endometriosis treated with progesterone.

Several reports suggest that women with endometriosis have a higher risk of spontaneous abortions when left untreated; however, these studies did not control for the presence of possible luteal phase defects. This study was designed to document the frequency of spontaneous abortions in women with endometriosis and ovulation defects treated prophylactically with progesterone, compared with similar patients without endometriosis. All the women had late luteal phase endometrial biopsies dating perfectly normal. Our findings show an increase in the rate of spontaneous abortions (25.7%) in women with endometriosis as compared with the entire group (3.8%). However, when the result for the group with endometriosis is compared with the subgroup of patients at diagnostic laparoscopy not showing endometriosis, the results are similar (30%). We conclude that when properly matched groups are compared, there is no increased risk of spontaneous abortions in women with endometriosis. Since we perform laparoscopies only in women failing to conceive after a reasonable number of seemingly normal cycles, the apparently high incidence of abortions in this group may be secondary to other factors that not only may lengthen the time needed for conception but also increase the abortion risk after conception.

Abortion, Spontaneous↗
PubMedDate not supplied

Rehydration of air-dried smears with normal saline. Application in fluid cytology.

Ninety fluid specimens (30 each of urine, ascitic and pleural fluid) were studied by preparing three comparable smears. One was air dried for Giemsa stain, one wet fixed in 95% ethanol and one dried on a hot plate at 37 degrees C, rehydrated in normal saline for 30 seconds and fixed in ethanol. The latter two were stained with Papanicolaou stain, and a comparison was made of the (1) retention of red blood cells, (2) retention of epithelial or mesothelial cells, and (3) cytologic preservation. The Giemsa-stained smear was used as a control for (1) and (2). Complete lysis of red blood cells was noted in the rehydration smears as compared with 70% red blood cell retention in the wet-fixed smears (P < .01). The rehydration smears retained 78% urothelial cells as compared with 55% in the wet-fixed smears (P < .01). For ascitic and pleural fluid the cell retention did not differ significantly. The wet-fixed smears scored better for overall cytologic preservation, but the difference was not significant. The rehydration smears showed a decrease in the chromaticity of staining, more flattened cell clusters and slight cell enlargement. The rehydration method was beneficial for urine and blood-stained body cavity fluids.

Ascitic Fluid↗