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Biomedical subjects

L Tan

Publications and source records attributed to L Tan.

At least 19 recordsLinked to original sources
PubMed1995

A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes.

We previously reported the cloning of a serine/threonine kinase, PAK (for p21 (Cdc42/Rac)-activated kinase), which binds to the Ras-related GTPases Cdc42Hs and Rac1 (Manser, E., Leung, T., Salihuddin, H., Zhao, Z-s., and Lim, L. (1994) Nature 367, 40-46). These p21 proteins together with RhoA comprise the Rho subfamily of proteins that are involved in morphological events. We now report the isolation of a rat cDNA encoding a 150-kDa protein, which specifically binds RhoA in its GTP form and contains an N-terminal serine/threonine kinase domain highly related to the human myotonic dystrophy kinase and a cysteine-rich domain toward the C terminus. The RhoA binding domain is unrelated to other p21 binding domains. Antibody raised against the kinase domain of the predicted protein, termed ROK alpha (for ROK alpha, RhoA-binding kinase), recognized a ubiquitous 150-kDa protein. The brain p150 purified by affinity chromatography with RhoA exhibited serine/threonine kinase activity. In cultured cells, immunoreactive p150 was recruited to membranes upon transfection with dominant positive RhoAV14 mutant and was localized with actin microfilaments at the cell periphery. These results are consistent with a role for the kinase ROK alpha as an effector for RhoA.

3T3 Cells↗
PubMed1995

Benign and malignant breast lesions: differentiation with echo-planar MR imaging.

PURPOSE: To quantify dynamic enhancement of breast lesions with echo-planar and conventional magnetic resonance (MR) imaging, to correlate these data with histologic findings and vessel density, and to evaluate MATERIALS AND METHODS: Twenty female patients with 22 breast lesions underwent conventional and MR echo-planar imaging T1 values, change in gadopentetate dimeglumine concentration, and extraction-flow products were calculated with echo-planar imaging data and were correlated with histologic findings and microvessel density. RESULTS: T1 values of cancers were not statistically significantly shorter. Cancers had more rapid uptake and higher extraction-flow products (P < .02). Sensitivity was 86% and specificity was 93% for diagnosis of malignancy. Microvessel density was higher for malignant lesions (P < .02) with an overall positive (not statistically significant) correlation between extraction-flow product and microvessel density. CONCLUSION: Echo-planar imaging appears promising for quantification of breast lesion enhancement. Microvessel data indicate that tumor angiogenesis affects enhancement.

Adolescent↗
PubMed1994

Radiotherapy in the treatment of malignant mesothelioma of the pleura, with special reference to its use in palliation.

Most patients presenting with malignant mesothelioma of the pleura (MMP) are only suitable for palliative treatment. Radiotherapy has not been shown to improve survival in patients with this disease, but is of use in the palliation of symptoms. In this retrospective review of 111 patients with MMP referred to the Peter MacCallum Cancer Institute, the palliative effect of radiotherapy was analysed. More than half of the patients whose response could be assessed had some symptomatic relief from the radiotherapy treatment. No dose-response relationship could be found.

Adult↗
PubMed1992

Cytokine-induced production of monocyte chemoattractant protein-1 by cultured human mesangial cells.

The infiltration of the glomerulus by monocyte-derived macrophages is an important step in the pathogenesis of glomerular injury. The factors regulating glomerular leukocyte traffic remain unknown. We postulated that the glomerular mesangial cell (MC) may participate in the development of glomerular inflammation through the production of the monocyte-specific chemotactic factor, monocyte chemoattractant protein-1 (MCP-1). Using a cell culture system, we found that human MC produced a basal level of monocyte chemotactic activity, which was significantly increased by the inflammatory cytokines IL-1 beta and TNF-alpha. This increase in bioactivity correlated with the increased expression of MCP-1 mRNA by cytokine-conditioned MC. The total chemotactic activity of MC-conditioned supernatants was reduced by more than 80% after immunoadsorption with a specific anti-MCP-1 antibody. Thus, MC could play a role in inflammatory glomerular conditions through the production of MCP-1.

Cells, Cultured↗
PubMed1992

Liposomes enhance the immunogenicity of reconstituted influenza virus A/PR/8 envelopes and the formation of protective antibody by influenza virus A/Sichuan/87 (H3N2) surface antigen.

Reconstituted influenza virus (A/PR/8 strain) envelopes (RIVE) and influenza virus (A/Sichuan/87 (H3N2) strain) surface antigens were entrapped in dehydration-rehydration vesicles (DRV liposomes) composed of egg phosphatidylcholine (PC) or distearoyl phosphatidylcholine (DSPC DRV) and equimolar (32 mumol) cholesterol. Entrapment values for RIVE were 31.2 (PC) and 29.4% (DSPC DRV) of the material used. Corresponding entrapment values for the A/Sichuan/87 strain antigens were 40.7 and 39.3%. Balb/c mice injected intramuscularly with PC or DSPC DRV liposomes containing 0.1 and 1.0 microgram RIVE exhibited primary (higher dose only) and secondary responses (IgG1) which were significantly higher than those obtained in mice injected with identical amounts of non-entrapped RIVE. Significantly higher secondary responses were also observed for the IgG2a and IgG2b subclasses. In experiments designed to assess the effectiveness of DRV liposomes as a carrier of influenza virus antigens in a potential vaccine, hamsters were immunized intramuscularly with 0.1, 0.5 and 5.0 micrograms of free or liposome-entrapped influenza A/Sichuan/87 surface antigens. Results showed increased haemagglutination inhibition (HI) antibody levels in terms of both primary (0.5 and 5.0 micrograms doses) and secondary (all doses) responses in the sera of animals treated with the liposomal formulations. DSPC compared with PC DRV exhibited greater adjuvanticity when the lower doses of antigens were used.

Adjuvants, Immunologic↗
PubMed1992

Processing of rat prolactin by rat tissue explants and serum in vitro.

Previous work has shown that enzymes from rat liver or mammary gland can cleave rat (r) PRL to form a two-chain derivative that yields approximately 16- and 7-kilodalton (kDa) fragments upon reduction. Both cleaved rPRL and the purified 16-kDa fragment have maintained biological activity. Thus, cleavage may be of physiological significance. To determine whether rPRL can be cleaved by intact cells, and to evaluate the extent to which rPRL processing is tissue specific and varies with physiological state, rPRL was incubated with slices of different tissues from cycling, midpregnant, or 15-day lactating rats. The molecular mass and relative abundance of rPRL and fragments of the hormone in the medium were determined using reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting with an antiserum to the 16-kDa fragment of rPRL. Parenthetically, the fragment that was previously identified as having a molecular mass of 16 kDa had the same mobility on reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis as the form that we designate as having a molecular mass of 14 kDa. Kidney, spleen, mammary gland and liver explants from pregnant rats processed PRL in qualitatively and quantitatively different ways. Mammary gland from lactating rats produced more of a 14-kDa fragment than liver or kidney slices from lactating rats, and the capacity to produce 14-kDa PRL by mammary gland from rats in different physiological states was as follows: pregnant greater than cycling greater than lactating. Fragments of 11 and 16 kDa were also produced, but only by mammary gland from lactating rats, and the latter only after 3 h of incubation. After a 2-h incubation, PRL-like immunoreactivity in lactating mammary gland medium was composed of 23-, 14-, and 11-kDa forms in the following relative amounts: 65 +/- 9, 17 +/- 1, and 10 +/- 5%, respectively. These results suggest that PRL is cleaved in a manner that varies with different tissues and physiological states; and thus, forms are produced that might be important mediators of PRL's biological actions on different target tissues. Medium conditioned by preincubation with mammary gland from lactating rats and clarified by 15,000 x g centrifugation had no PRL-cleaving activity at pH 7.4, but gained activity when the pH was lowered, with maximal activity at pH 2.6-3.0. When heated to 85 C for 15 min, such medium had no activity at pH 3.0.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Recombinant human tumor necrosis factor-beta entrapped in liposomes formed by a modification of the dehydration-rehydration method retains potent cytotoxic activity on L929 cells in vitro.

Recombinant human tumor necrosis factor-beta (rhTNF-beta) may be encapsulated with high efficiency in phosphatidylcholine and distearoylphosphatidylcholine liposomes, with entrapment values of 93.4% and 92.3%, respectively, by first entrapping the substance in multilamellar vesicles using a high solute-to-phospholipid ratio followed by freeze-drying and then rehydration. The entrapped cytokine retains potent cytotoxic activity on L929 cells in vitro, causing 100% cytotoxicity, equal to that of free rhTNF-beta at a concentration of about 5 x 10(-8) g/ml.

Animals↗
PubMed1992

[Atmosphere pollution by sulfur dioxide during processing of zirantong].

This paper reports the colorimetric determination of total SO2 in Zirantong by the method of rosaniline hydrochlorid. Samper of processed Zirantong from the pharmacy have been analyzed and the quality specifications established. Optimum conditions for processing have been chosen and a procedure has been proposed for the recovery of the poisonous matter SO2 which is then transformed into a beneficial material.

Air Pollution↗
PubMed1991

Regions of the T cell receptor alpha and beta chains that are responsible for interactions with CD3.

The T cell antigen receptor consists of the Ti alpha/beta heterodimer which recognizes antigen, and the associated CD3 chains, thought to be involved in signal transduction. To understand the nature of the interaction between Ti and CD3, chimeric molecules which included the COOH-terminal segments of Ti alpha or beta linked to the extracellular segment of CD8, were transfected into a mutant T cell deficient in Ti beta chain expression and cell surface CD3. Both chimeric chains were required to express the chimeric Ti and to restore CD3 surface expression. CD8/Ti and CD3 cointernalized and coimmunoprecipitated. Stimulation of the chimeric receptor induced transmembrane signaling events and cell activation. These results demonstrate that the Ti alpha and beta COOH termini containing the transmembrane domains are sufficient for structural and functional coupling of Ti to CD3.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Predicting recovery of facial nerve function following injury from a basilar skull fracture.

Twenty-five patients with posttraumatic facial nerve palsy were studied. Partial recovery of function had occurred in 95% of these patients by 18 months after injury. At 5 months posttrauma, there was some recovery in 92.5% of those with a partial lesion compared with 10% of those with a complete lesion. This difference attains statistical significance. Complete recovery of nerve function had occurred by 10.5 months in 53.5% of the patients; in 62% of patients with a partial lesion, complete recovery had occurred by 4 months compared with 0% in those with a complete lesion. This difference also attains statistical significance. There was no statistically significant difference in recovery of function between patients with an immediate as opposed to a delayed onset of facial nerve palsy. It was determined that the degree of palsy had a statistically significant influence on recovery of facial nerve function, whereas the time of onset did not. The data presented support a conservative approach to these injuries and it is recommended that the possibility of surgical treatment should be entertained in patients with complete facial palsy persisting for 12 to 18 months after injury.

Adolescent↗
PubMed1991

Comparison of the immune response against polio peptides covalently-surface-linked to and internally-entrapped in liposomes.

The adjuvanticity of liposomes on two different modes of presentation of polio virus subunit peptides was demonstrated by incorporating the poorly immunogenic synthetic polio peptides, W1 and W2, into the internal space of and covalently-linked to the surface of dehydration-rehydration vesicles (DRV). It was found that for both peptides, liposome association in either mode boosted the primary and secondary IgG1 responses against 5 micrograms peptide as compared to controls in which free peptide was administered. Surface-linkage of peptides (both W1 and W2) exhibited an initially more rapid rise in antibody levels, as compared to internal entrapment of the peptides, but elicited no observable secondary response. However, although encapsulated W1 showed a milder primary response when compared to the surface-linked formulation, it later elicited a strong secondary response. These results suggested that it may be advantageous to administer liposomal virus subunit vaccines in both surface-linked and internally entrapped formulations to achieve adequate initial antibody levels followed by an anamnestic response.

Adjuvants, Immunologic↗
PubMed1991

A novel positively-charged lipid 1,2-bis(hexadecylcycloxy)-3-trimethyl aminopropane (BisHOP) enhances the adjuvant effect of liposomes on encapsulated tetanus toxoid.

A novel positively charged lipid, 1,2-bis(hexadecylcycloxy)-3-trimethylaminopropane-HCl (BisHOP), when incorporated into the bilayers of phosphatidylcholine (PC) and distearoyl phosphatidylcholine (DSPC) dehydration-rehydration vesicles (DRV), was shown to have a powerful effect in enhancing the IgG1 response to tetanus toxoid encapsulated within the liposomes. The adjuvant effect was significantly greater when 20% BisHOP was incorporated as compared to 10% incorporation and to control PC and DSPC DRV. Plain, uncharged DSPC DRV were found to have a greater adjuvant effect than plain PC DRV on the entrapped tetanus toxoid after a single intramuscular injection. Even though antibody levels at 8 weeks post-injection were similar for 20% BisHOP PC and DSPC DRV, the rate of rise of antibody titres was more rapid for 20% BisHOP DSPC than for 20% BisHOP PC DRV. These results suggest that faster and higher titers of antibodies may be obtained by optimal manipulation of the charged and non-charged lipid components of liposomes.

Adjuvants, Immunologic↗
PubMed1991

A study of the efficacy of liposomes in comparison to new and established adjuvants in potentiating the antibody response against hepatitis B virus surface antigen.

The dehydration-rehydration vesicle (DRV) method was used to encapsulate hepatitis B surface antigen (HBsAg) in phosphatidylcholine (PC) and distearoyl phosphatidylcholine (DSPC) liposomes giving entrapment values of 31.7% and 33.1% respectively. A comparison of antibody levels, as determined by ELISA, in the primary and secondary immune responses in mice immunized twice with 1 microgram HBsAg free, or in formulations of PC DRV, DSPC DRV, Syntex Adjuvant Formulation (SAF), alum and Freund's Complete Adjuvant (FCA) showed that by far, FCA was the best adjuvant in both the primary and secondary IgG1, IgG2a and IgG2b responses. In the secondary response, apart from FCA, DSPC DRV and SAF were equally efficacious and better adjuvants than alum and PC DRV for the IgG2a and IgG2b subclasses. SAF was a better adjuvant for HBsAg than alum, DSPC DRV and PC DRV (in descending order of efficacy) in the secondary IgG1 response.

Alum Compounds↗
PubMed1990

Use of a nasal continuous positive airway pressure mask in the treatment of postoperative atelectasis in aortocoronary bypass surgery.

Pulmonary oxygen transfer, defined by PaO2/FIO2, and radiologic presence of atelectasis were measured pre-, intra-, and postoperatively to postoperative day 9 in elective cardiac aortocoronary bypass surgical patients, who were randomly allocated either to receive 18 h PEEP while on the ventilator followed by 12 h of nasal continuous positive airway pressure (nasal CPAP) or to be control subjects. The two groups were comparable in age, sex, forced expiratory volume in 1 sec (FEV1), the ratio of FEV1 over forced vital capacity (FVC), time on pump, units of blood transfused, New York Heart Association grading, and cardiac performance indices. The PaO2/FIO2 was significantly (p less than .05) better from half an hour after extubation until 24 h postextubation in the nasal CPAP group, but was decreased for the remainder of the study in both groups. Incidence of atelectasis/consolidation was not different in both groups during the study period. We conclude that nasal CPAP is well tolerated as a treatment of hypoxemia in the immediate postoperative period of aortocoronary bypass patients. CPAP does not change the course of postoperative atelectasis.

Aged↗