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Biomedical subjects

Y C Lo

Publications and source records attributed to Y C Lo.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of a new transcutaneous bilirubinometer in Chinese newborns.

OBJECTIVE: To evaluate the use of a new transcutaneous bilirubinometer (JM-103 Minolta Airshields) for detection of hyperbilirubinaemia in term or near-term healthy Chinese newborns. METHODS: Transcutaneous bilirubin (TcB) was used to screen for severe hyperbilirubinaemia in newborn infants. Blood was taken for total serum bilirubin (TSB) measurement if the initial TcB level was higher than the 40th centile in Bhutani's nomogram. Paired TcB and TSB results were then reviewed over 6 months. The correlation as well as the mean difference between the two methods were calculated. The clinical application of TcB with Bhutani's nomogram in the prediction of severe hyperbilirubinaemia in low-risk, medium-risk and high-risk thresholds for phototherapy was also analysed. RESULTS: 997 paired TcB and TSB measurements were evaluated in term or near-term newborns. TcB was significantly correlated with TSB, with a correlation coefficient of 0.83 (p<0.001). Their mean difference was 21.7 micromol/l (SD 21.2, p<0.001), with the 95% limits of agreement between -19.9 and 63.3 micromol/l. In both low-risk and medium-risk thresholds for phototherapy, using the 75th centile of Bhutani's nomogram as threshold, TcB could identify all cases and had a sensitivity and negative predictive value of 100% each, a specificity of 56% and positive predictive value of 23%. For high-risk cases, using the 75th centile as cut-off, the sensitivity and negative predictive value were reduced to 86.7% and 97.0%, respectively. CONCLUSION: An accurate point-of-care bilirubin analyser facilitates bilirubin screening and avoids unnecessary blood tests. Although using the transcutaneous bilirubinometer JM-103 might result in a significant difference between TcB and TSB measured in Chinese newborns, combining the use of TcB and the 75th centile in Bhutani's nomogram as the cut-off level can identify all cases of significant hyperbilirubinaemia.

Bilirubin↗
PubMed2006

The effect of radiation therapy on normal tissue function.

As more patients are treated for their primary malignancy with cure or increased disease-free intervals, injury to normal tissues will become more detectable and an important endpoint for study. Future protocols will probably be modified based on toxicity endpoints. In Hodgkin's disease, current protocols use response-based treatment strategies to limit therapy. The objective is to provide the same level of tumor control and follow normal tissue endpoints for outcome analysis. DVH analysis has improved the ability to analyze endpoint data for normal tissues. These image-guided platforms will provide the infrastructure needed to continue efforts in improving the delivery of radiation therapy.

Dose-Response Relationship, Radiation↗
PubMed2005

San-Huang-Xie-Xin-Tang attenuates inflammatory responses in lipopolysaccharide-exposed rat lungs.

In this study, the potential anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on LPS-induced lung injury were investigated and compared to the profile of dexamethasone (DEXA) in a pre-clinical animal model. Post-treatment with SHXT (75 mg/kg), baicalin (1.5 mg/kg) and DEXA (0.5 mg/kg), significantly inhibited LPS-induced hypotension, lung edema and acute survival rates. Western blotting analysis results indicated that all of them significantly inhibited LPS-induced iNOS, TGF-beta, p38MAPK, and ICAM-1 expressions in the lung tissues. Results from ELISA analysis showed that SHXT, baicalin and DEXA all decreased plasma levels of IL-1beta, TNF-alpha, and MCP-1 caused by LPS. Based on these findings, SHXT and baicalin decreased plasma concentrations of IL-1beta, TNF-alpha, MCP-1, and expressions of TGF-beta, ICAM-1, phosphorylated p38 MAPK, and iNOS, which were associated with lung injury and lethality. These evidences indicated that SHXT and baicalin showed strong anti-inflammatory activity, similar to that observed for DEXA, and therefore implicated that herbal SHXT might be therapeutically useful for the treatment of endotoxic lung injury.

Animals↗
PubMed2004

Forward-planned, multiple-segment, tangential fields with concomitant boost in the treatment of breast cancer.

We report on the utility of forward-planned, 3-dimensional (3D), multiple-segment tangential fields for radiation treatment of patients with breast cancer. The technique accurately targets breast tissue and the tumor bed and reduces dose inhomogeneity in the target. By decreasing excess dose to the skin and lung, a concomitant boost to the tumor bed can be delivered during the initial treatment, thereby decreasing the overall treatment time by one week. More than 120 breast cancer patients have been treated with this breast conservation technique in our clinic. For each patient, a 3D treatment plan based upon breast and tumor bed volumes delineated on computed tomography (CT) was developed. Segmented tangent fields were iteratively created to reduce "hot spots" produced by traditional tangents. The tumor bed received a concomitant boost with additional conformal photon beams. The final tumor bed boost was delivered either with conformal photon beams or conventional electron beams. All patients received 45 Gy to the breast target, plus an additional 5 Gy to the surgical excision site, bringing the total dose to 50 Gy to the boost target volume in 25 fractions. The final boost to the excision site brought the total target dose to 60 Gy. With minimum follow-up of 4 months and median follow-up of 11 months, all patients have excellent cosmetic results. There has been minimal breast edema and minimal skin changes. There have been no local relapses to date. Forward planning of multi-segment fields is facilitated with 3D planning and multileaf collimation. The treatment technique offers improvement in target dose homogeneity and the ability to confidently concomitantly boost the excision site. The technique also offers the advantage for physics and therapy staff to develop familiarity with multiple segment fields, as a precursor to intensity-modulated radiation therapy (IMRT) techniques.

Breast Neoplasms↗
PubMed2001

Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-alpha.

The binding of tumor necrosis factor alpha (TNF-alpha) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein-protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-alpha to TNFRc1 (IC(50) = 50 nM) and also blocked TNF-stimulated phosphorylation of Ikappa-B in Ramos cells (IC(50) = 600 nM). This compound did not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 microM. Detailed evaluation of this and related molecules revealed that compounds in this class are "photochemically enhanced" inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity (ca. 40-100 microM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-alpha to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-alpha-TNFRc1 interaction.

Antigens, CD↗
PubMed2001

Defining the risk of developing grade 2 proctitis following 125I prostate brachytherapy using a rectal dose-volume histogram analysis.

OBJECTIVE: To determine the rectal tolerance for developing Grade 2 radiation proctitis after 125I prostate implantation based on the rectal dose-volume histogram. METHODS AND MATERIALS: Two hundred twelve patients with T1-T2 prostate cancer underwent 125I implantation without external beam irradiation. One month after the procedure, all patients underwent CT-based postimplant dosimetry (3-mm abutting slices). The rectal volumes, defined by an inner and outer wall, were determined from 9 mm above the seminal vesicles to 9 mm below the prostate apex. All doses were calculated by TG43 formalism. The prostate prescription dose was 160 Gy. A dose response analysis was undertaken for volumes of rectal tissue receiving a given dose. Dose levels examined were 80 Gy, 100 Gy, 120 Gy, 140 Gy, 160 Gy, 180 Gy, 200 Gy, 220 Gy, and 240 Gy. Grade 2 proctitis was defined as rectal bleeding occurring at least once a week for a minimum period of one month. The risk of proctitis was calculated using actuarial methods. For each dose level, a critical volume cutpoint was chosen to define a low and high volume group of patients. The cutpoint was determined based on two goals: minimizing thep value and finding a < or =5% risk of proctitis in the low volume group. Patients were followed from 12 to 61 months (median: 28 months) after implantation. RESULTS: Twenty-two patients developed Grade 2 proctitis: 14% within the first year, 72% between the first and second year, and 14% during the third year after the implant date. After the third year postimplantation, no cases of proctitis were reported. Proctitis was found to be significantly volume dependent for a given dose. The prescription dose (160 Gy) delivered to < or =1.3 cc of rectal tissue resulted in a 5% rate of proctitis at 5 years vs. 18% for volumes >1.3 cc (p = 0.001). Similar results were found for all doses examined. As the rectal volume receiving the prescription dose (160 Gy) increased, so did the proctitis rate: 0% for < or =0.8 cc, 7% for >0.8-1.3 cc, 8% for >1.3-1.8 cc, 24% for >1.8-2.3 cc, and 25.5% for >2.3cc (p = 0.002). CONCLUSIONS: Rectal dose-volume histogram analysis is a practical and predictive method of assessing the risk of developing Grade 2 proctitis after 125I prostate implantation. Delivered dose should be kept below defined rectal volume thresholds to minimize this risk. This information can allow one to decrease rectal morbidity by modifying prostate implant technique.

Aged↗
PubMed2001

Design of transgenes for efficient expression of active chimeric proteins on mammalian cells.

Heterologous proteins expressed on the surface of cells may be useful for eliciting therapeutic responses and engineering new extracellular properties. We examined factors that control the membrane targeting of alpha-fetoprotein (AFP) and a single-chain antibody (scFv). Chimeric proteins were targeted to the plasma membrane by employing the transmembrane domain (TM) and cytosolic tail of murine CD8O (B7-1), the TM of the human platelet-derived growth factor receptor (PDGFR), the glycosylphosphatidylinositol anchor encoded by the C-terminal extension of decay-accelerating factor (DAF), and the TM of the H1 subunit of the human asialoglycoprotein receptor (ASGPR). AFP chimeric proteins containing the B7, DAF, ASGPR, or PDGFR targeting domains displayed half-lives of 12.2, 3.8, 2.4, and 1.6 h, respectively. The newly synthesized B7 chimera was rapidly transported and remained on the cell surface. Glycosylphosphatidylinositol-anchored chimeras reached the surface more slowly and significant amounts were released into the culture medium. PDGFR TM chimeras were rapidly degraded, whereas ASGPR chimeras were retained in the endoplasmic reticulum (ER). The surface expression of both AFP and scFv chimeric proteins followed the order (highest to lowest) of B7 > DAF >> PDGFR. Introduction of a dimerization domain (hinge-CH(2)-CH(3) region of human IgG1) between scFv and TM dramatically reduced cleavage of the chimeric protein, increased surface expression, and produced biologically active scFv. Our results indicate that transgenes designed for the expression of active scFv on cells should incorporate a TM that does not undergo endocytosis, include an intact cytoplasmic domain, and possess a spacer to reduce cleavage and retain biological activity.

3T3 Cells↗
PubMed2001

Recombinant expression and characterization of the Candida rugosa lip4 lipase in Pichia pastoris: comparison of glycosylation, activity, and stability.

Although Candida rugosa utilizes a nonuniversal serine codon (CUG) for leucine, it is possible to express lipase genes (LIP) in heterologous systems. After replacing the 19 CUG codons in LIP4 with serine codons by site-directed mutagenesis, a recombinant LIP4 was functionally overexpressed in Pichia pastoris in this study. This recombinant glycosylated lipase was secreted into the culture medium with a high purity of 100 mg/liter in a culture broth. Purified recombinant LIP4 had a molecular mass of 60 kDa, showing a range similar to that of lipase in a commercial preparation. Since LIP4 has only a glycosylation site at position Asn-351, this position may also be the major glycosylation site in C. rugosa lipases. Although the thermal stability of recombinant LIP4 significantly increased from 52 to 58 degrees C after glycosylation, there were no significant differences in the catalytic properties of recombinant glycosylated lipase from P. pastoris and the unglycosylated one from Escherichia coil. These two recombinant LIP4s showed higher esterase activities toward long-chain ester (C16 and C18) and exhibited higher lipase activities toward unsaturated and long-chain lipids. In addition, LIP4 does not show interfacial activation as compared with LIP1 toward lipid substrates of tributyrin and triolein. These observations demonstrated that LIP4 shows distinguished catalytic activities with LIP1 in spite of their high sequence homology.

Candida↗
PubMed2001

Prevention of cerebral vasospasm by a capsaicin derivative, glyceryl nonivamide, in an experimental model of subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a major complication in patients suffering from SAH. In our previous study, we reported that stimulating vascular K(+) channel activity prevented the development of cerebral vasospasm. Recent evidence indicates that glyceryl nonivamide (GLNVA), a capsaicin derivative, has a vasorelaxant effect on the aortic vascular smooth muscle due to the release of coronary calcitonin gene-related peptide, which in turn stimulates K(+) channel opening. The purpose of the present study was to examine the preventive effects of GLNVA on vasospasm. METHODS: New Zealand white rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. GLNVA or vehicle was injected intrathecally immediately after the induction of SAH. All animals were killed by perfusion-fixation at 48 hours after SAH. The basilar arteries were removed and sectioned, and their cross-sectional areas were measured. RESULTS: The average cross-sectional areas of basilar arteries were reduced by 69% and 71% in the SAH only and SAH plus vehicle groups, respectively, when compared with the healthy controls. After treatment with 0.35, 1.75, and 3.5 mg/kg GLNVA in rabbits subjected to SAH the average cross-sectional area was decreased by 46%, 12% and 2%, respectively, when compared with the healthy controls. The protective effect of GLNVA achieved statistical significance at all dosages. Morphologically, corrugation of the internal elastic lamina of vessels was often observed in the vehicle-treated group, but was not prominent in the GLNVA-treated groups or healthy controls. CONCLUSION: The findings showed that GLNVA dose-dependently attenuated cerebral vasospasm after SAH in the rabbit. These results suggest that intrathecal administration of GLNVA could be an effective strategy for preventing cerebral vasospasm after SAH.

Animals↗
PubMed2001

A new aspect of view in synthesizing new type beta-adrenoceptor blockers with ancillary antioxidant activities.

A series of vanilloid-type beta-adrenoceptor blockers derived from antioxidant traditional Chinese herbal medicines were synthesized and tested for their antioxidant and adrenoceptor antagonistic activities. They all possessed significant beta-adrenoceptor blocking activities under in vitro experiments and radioligand binding assays. In addition, some compounds were further examined in in vivo tests and produced antagonist effects matching that of propranolol and labetalol by measurements of antagonism toward (-)isoproterenol-induced tachycardia and (-)phenylephrine-induced pressor responses in anesthetized rats. Furthermore, all of the compounds had antioxidant effects inherited from their original structures. In conclusion, compound 11 had the most potent beta-adrenoceptors blocking activity, 12 and 13 possessed high cardioselectivity, whereas 14, 15 and 16 possessed additional alpha-adrenoceptor blocking activity and 15 is the most effective antioxidant of all. The antioxidant activity may be due to their alpha and beta unsaturated side chain at position 1 and ortho-substituted methoxy moiety on 4-phenoxyethylamine.

Adrenergic beta-Antagonists↗
PubMed2001

Miniature multileaf collimator as an alternative to traditional circular collimators for stereotactic radiosurgery and stereotactic radiotherapy.

PURPOSE: To evaluate the miniature multileaf collimator (MMLC) as an alternative to traditional circular collimators for radiosurgery. MATERIALS AND METHODS: 'Circular' fields were created with the Radionics MMLC (leaf width 3.53 mm at isocenter). Beam data, including tissue maximum ratios, output factors, penumbrae and isodose distributions of these fields were measured. These were compared to the Radionics circular collimators traditionally used for radiosurgery. The MMLC data were input to the XKnife Treatment Planning System. Treatment plans were completed and evaluated using both the MMLC 'circular' fields and the circular collimators. RESULTS: MMLC fields using 3, 5, 7, 9, 11, and 13 leaves on each side of the Radionics MMLC were created to approximate circular fields. The TMRs are essentially identical to those of comparable-size circular collimators. Measured at isocenter at 5-cm depth for 6 MV, the 80-20% penumbra widths are comparable to circular collimators, but are increased by as much as 1 mm at the leaf intersections (steps) where scalloping occurs. Isodose distributions were matched to those of circular collimators with comparable 50% isodose widths. Treatment plans for the MMLC 'circular' fields with four arcs (totaling 360 degrees) are essentially identical to those of comparable circular collimators. Dose-volume histograms revealed clinically insignificant differences between the two in doses to the target, to the volume surrounding the target, and to adjacent critical normal tissues. There is very little discrepancy between the dose distribution calculated with the approximated MMLC fields and with those of simulated arcs with the actual MMLC fields. CONCLUSIONS: With the MMLC simulating circular fields, dose distributions may be obtained which are essentially identical to comparable-size circular collimators. The mechanical accuracy of the MMLC is as good as that of the circular collimators, and the leakage dose is less. The diameter of 'circular' fields is limited by the MMLC leaf width to 1 cm and greater in increments of 7 mm. Attention needs to be paid to mechanical collisions because the MMLC is bulkier than the circular collimators.

Humans↗
PubMed2000

Postimplant dosimetry for (125)I prostate implants: definitions and factors affecting outcome.

OBJECTIVE: An analysis of CT-based dosimetry was performed to assess the efficacy of the real time method of prostate implantation, explore the relationship of various dose descriptions and determine implant factors affecting outcome. METHODS AND MATERIALS: Between 7/95 and 8/99, 297 patients underwent (125)I implants for T1-T2 prostate cancer and had CT-based dosimetry performed (TG43 formalism). Dosimetry was performed 1 month postimplant. Using a dose-volume histogram, doses delivered to 100%, 95%, 90%, and 80% of the prostate (D100, D95, D90, D80, respectively) as well as percentages of the gland receiving 240 Gy, 160 Gy, 140 Gy (V240, V160, V140, respectively) were reported. Correlations between the various dose parameters and D90 were generated. The effect of the number of seeds implanted, seeds/volume, prostate volume, experience as assessed by time (8/01/99-date of implant), ultrasound probe (mechanical sector vs. dual phased electronic), and the ratio of the CT dosimetry prostate volume/ultrasound implant volume (CT/US vol) were analyzed. RESULTS: The median D100, D95, D90, and D80 values were 10,200 cGy, 15,655 cGy, 17,578 cGy, and 19,873 cGy, respectively. The median V240, V160, and V140 were 56%, 94%, and 98%, respectively. Correlations of dose descriptions found a close relationship of D95, D80, V240, V160, and V140 with D90 with r values of 0.928, 0.973, 0.911, 0.816, and 0.733, respectively. D100 correlated poorly with D90 (r = 0.099). Using a stepwise regression analysis, CT/US vol ratio, prostate volume, and seed number were the only significant factors affecting D90 with CT/US vol ratio having the greatest effect. The dual-phased electronic probe was associated with fewer D90 values of less than 140 Gy (2%) compared to the mechanical sector probe (14%) (p = 0.02). CONCLUSION: CT-based dosimetry results reveal the real-time implant technique to be an effective method of prostate implantation. Factors associated with more precise implantation, such as decreased postimplant edema, new technology, and increased number of seeds will lead to higher D90 values.

Brachytherapy↗
PubMed2000

The epidermal growth factor receptor is required to maintain the proliferative population in the basal compartment of epidermal tumors.

Previous studies using keratinocytes from epidermal growth factor receptor (EGFR)-deficient mice revealed that the EGFR is not required for papilloma formation initiated by a mutant rasHa gene, although the tumors that develop are very small (A. A. Dlugosz et aL, Cancer Res., 57: 3180-3188, 1997). The current study used a combination of bromodeoxyuridine pulse-chase, proliferating cell nuclear antigen distribution, and differentiation marker analysis to reveal the following: (a) the EGFR was required to maintain the proliferative population in the basal cell compartment of papillomas; (b) in the absence of EGFR, cycling tumor cells migrated into the suprabasal compartment and initiated the differentiation program prematurely; and (c) these changes were associated with cell cycle arrest. Further analysis of v-rasHa-transformed EGFR-deficient keratinocytes in vitro indicated that such cells migrated more on and attached less to extracellular matrix components. Together, these studies reveal that an essential function for the EGFR pathway in squamous tumors is to maintain a proliferative pool of basal cells and prevent premature terminal differentiation.

Animals↗
PubMed2000

Intensity modulation for breast treatment using static multi-leaf collimators.

PURPOSE: To achieve more uniform dose distributions in breast cancer treatment using multiple sets of multi-leaf collimator (MLC) defined fields. Dose uniformity for many breast cancer patients can be significantly improved by using two or more sets of portals and the "hot" regions of a traditional treatment can be significantly reduced. METHODS AND MATERIALS: Patients for breast cancer treatment are immobilized with alpha cradle in the traditional arm-up position and have a CT scan in the treatment position. The target volume is delineated on the 5-mm thick CT slices that are obtained from the lower neck to well below the breast target volume. Medial and lateral tangential fields at conventional gantry angles are designed with the aid of digitally reconstructed radiographs (DRRs). The MLC, without collimator rotation, is used to shape the field to spare as much lung as possible. The wedges and relative weights of the beams are optimized to provide the best dose uniformity. For the patients with large dose inhomogeneity, a second set of fields is designed. The weight of the original set of fields is reduced (usually to approximately 90%) so that the "original hot" regions receive the prescription dose; the second set of fields delivers a supplemental dose to the "cold" region, typically approximately 10% of the total dose. The second set of fields has the same beam parameters but "treat" only the part of breast tissue that is "cool." Presently, the design of the reduced field is an iterative process. The process can be extended to more than two sets of portals to obtain the desired dose uniformity. RESULTS: With 3D planning and multiple MLC fields, dose uniformity in the treatment of breast patients was improved from 7%-22% to approximately 7%-15%. The volume receiving these high doses decreased significantly and shifted from the lung to the target. By keeping the gantry angles and wedges the same for the multiple fields, treatments can be delivered quickly and reliably. The internal mammary nodes (IM) can also be treated without including significant amount of lung or heart in the field. CONCLUSION: Dose uniformity can be significantly improved by using this intensity modulation technique to treat certain breast patients. With these static MLC fields creating the intensity modulation, the dose uniformity to the breast can be significantly improved and the hot region in lung reduced. There is no increase in setup complexity. The small increase in treatment time is insignificant.

Breast Neoplasms↗
PubMed2000

Lipid solubility of vasodilatory vanilloid-type beta-blockers on the functional and binding activities of beta-adrenoceptor subtypes.

Various vanilloid-type beta-adrenoceptor blockers were studied on guinea pig right atrium and trachea and rat colon. In addition, we also investigated their beta(1)-, beta(2)-, and beta(3)-adrenoceptor binding affinities. All these beta-adrenergic antagonists inhibited (-)isoproterenol-induced positive chronotropic effects of the right atrium and tracheal relaxation responses in a concentration-dependent manner. Some of these agents prevented the inhibition of rat colon spontaneous motility by (-)isoproterenol. Of the agents tested, we found that ferulidilol, eugenodilol, eugenolol, isoeugenolol, and ferulinolol, as well as propranolol and metoprolol, possessed beta(3)-adrenoceptor blocking activities, others were nearly without effectiveness. Furthermore, the binding characteristics of vanilloid-type beta-adrenergic antagonists were evaluated in [3H]CGP-12177, a beta(1)/beta(2)-adrenoceptor blocker and a beta(3)-adrenoceptor agonist, binding to beta(1)-, beta(2)-, and beta(3)-adrenoceptor sites in rat ventricle, lung, and interscapular brown adipose tissue (IBAT) membranes, respectively. Eugenodilol, eugenolol, metoprolol, isoeugenolol, and ferulinolol were less potent than both propranolol and ferulidilol in competing for the beta(3)-adrenoceptor binding sites. From the results of in vitro functional and binding studies, we suggested that propranolol, ferulidilol, eugenodilol, eugenolol, metoprolol, isoeugenolol, and ferulinolol all possessed beta(3)-adrenoceptor blocking activities. On the other hand, we also found that eugenodilol, eugenolol, metoprolol, isoeugenolol, and ferulinolol had a low lipid solubility in comparison with propranolol and ferulidilol. In conclusion, we proposed that beta(3)-adrenoceptor antagonistic actions of these vanilloid-type beta-blockers were positively correlated with their lipid solubility.

Adrenergic beta-Agonists↗
PubMed2000

Activation of lymphocytes by anti-CD3 single-chain antibody dimers expressed on the plasma membrane of tumor cells.

Activation of cytotoxic T cells without MHC restriction was attempted by expressing single-chain antibodies (scFv) against CD3 on the surface of tumor cells. A chimeric protein consisting of a scFv of mAb 145.2C11, the hinge-CH2-CH3 region of human IgG1, and the transmembrane and cytosolic domains of murine CD80 formed disulfide-linked dimers on the plasma membrane of cells and specifically bound lymphocytes. Anti-CD3 scFv dimers expressed on the cell surface induced CD25 (IL-2 receptor alpha-chain) expression and proliferation of splenocytes. CT26 tumor cells engineered to express surface scFv dimers (CT26/2C11) also induced potent lymphocyte cytotoxicity with or without addition of exogenous IL-2. Splenocytes activated by CT26/2C11 cells also killed wild-type CT26 cells, indicating that activated splenocytes could kill bystander tumor cells. Immunization of BALB/c mice with irradiated CT26/2C11 cells did not protect against a lethal challenge of CT26 cells, suggesting that systemic immunity was not induced. However, the growth of CT26 tumors containing 50% CT26/2C11 cells was significantly retarded compared with CT26 tumors, whereas CT26/2C11 tumors did not grow in syngeneic mice. These results suggest that expression of anti-CD3 scFv dimers on tumors may form the basis for a novel therapeutic strategy for tumors that exhibit defects in antigen processing or presentation. Gene Therapy (2000) 7, 339-347.

Animals↗
PubMed2000

Crystallization and preliminary X-ray crystallographic analysis of thioesterase I from Escherichia coli.

The Escherichia coli thioesterase I specifically catalyzes the deacylation of fatty acyl-CoA thioesters, especially those with long acyl groups (C(12)-C(18)). Single crystals of thioesterase I (E.C. 3. 1.2.2) from E. coli have been obtained using methoxypolyethylene glycol 5000 (PEG-MME 5K) as a precipitant at room temperature in 21 d. The crystals belong to the tetragonal space group P4(1)2(1)2 or its enantiomorph P4(3)2(1)2, with unit-cell parameters a = b = 50.85 (7), c = 171.5 (1) A. The crystals diffract to beyond 2.4 A resolution. There is one molecule of molecular weight 20.5 kDa in the asymmetric unit, with a solvent content of 55%.

Amino Acid Motifs↗