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Biomedical subjects

L Tan

Publications and source records attributed to L Tan.

At least 73 records · Page 4Linked to original sources

Feasibility study of an ultrasound contrast agent (levovist) in color Doppler imaging of liver neoplasms.

The purpose of this study was to determine the efficacy of using an ultrasound contrast agent (levovist) to enhance the color Doppler imaging of liver neoplasms. Thirty patients with hepatic tumors were enrolled in this study. After intravenous administration of levovist, the color Doppler signals of normal hepatic vessels were enhanced. In various hepatic tumors, the different patterns of tumor vascularity were observed, which had not been demonstrated in conventional non-contrast color Doppler imaging. In 11 of 16 patients with hepatocarcinoma, additional color Doppler signals were observed in the central part of the tumors. On the contrary, 3 patients with metastatic liver lesions the enhanced color Doppler signals appear only at the peripheral of tumors. A typical rim-like color enhancement was seen in 2 of the 3 cases. In six patients with hepatic hemangiomas contrast-enhanced color Doppler imaging demonstrated the blood vessels at the margin of the neoplasms. Contrast-enhanced color Doppler imaging improves the visualization of the hepatic neoplasm vascularity. This technique holds great promise for detecting small liver tumors and differentiating hepatic neoplasms.

Adult↗

Tissue-specific up-regulation of B7-1 expression and function during the course of murine relapsing experimental autoimmune encephalomyelitis.

B7/CD28-mediated costimulation is a promising target for therapeutic intervention in autoimmune diseases. However, studies addressing the differential functional roles of B7-1 and B7-2 in several autoimmune models have resulted in conflicting data, perhaps due to the temporal dynamics of B7-1 and B7-2 surface expression on different cell types and/or at different sites during an autoimmune response. We examined the temporal expression of B7 costimulatory molecules in the CNS and in various lymphoid organs during the course of murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE). Following immunization of SJL mice with the immunodominant proteolipid protein epitope, PLP139-151, surface expression of B7-1 was up-regulated on B cells, T cells, and macrophages, relative to B7-2, on CNS-infiltrating cells and on splenocytes. Similar enhancement in splenic B7-1 expression could be induced in SJL mice by the adoptive transfer of PLP139-151-specific cells or by immunization with CFA alone. These changes were not observed on lymph node cells, including those isolated from lymph nodes draining the immunization site, which maintained the predominant B7-2 expression pattern seen in naive mice. These phenotypic expression patterns correlated with the functional predominance of B7-1 in costimulating T cell activation when employing APCs from the spleen or CNS of mice with ongoing R-EAE, while B7-2 remained functionally predominant on lymph node APCs. Variation of phenotypic expression and functional dominance of costimulatory molecule expression in different lymphoid compartments during an active inflammatory autoimmune response has important implications in immune regulation, autoimmune pathogenesis, and therapeutic strategies.

Animals↗

Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo.

Primary infection with virus can stimulate a vigorous cytotoxic T cell response. The magnitude of the antigen-specific component versus the bystander component of a primary T cell response remains controversial. In this study, we have used tetrameric major histocompatibility complex-peptide complexes to directly visualize antigen-specific cluster of differentration (CD)8+ T cells during the primary immune response to Epstein-Barr virus (EBV) infection in humans. We show that massive expansion of activated, antigen-specific T cells occurs during the primary response to this virus. In one individual, T cells specific for a single EBV epitope comprised 44% of the total CD8+ T cells within peripheral blood. The majority of the antigen-specific cells had an activated/memory phenotype, with expression of human histocompatibility leukocyte antigen (HLA) DR, CD38, and CD45RO, downregulation of CD62 leukocyte (CD62L), and low levels of expression of CD45RA. After recovery from AIM, the frequency of antigen-specific T cells fell in most donors studied, although populations of antigen-specific cells continued to be easily detectable for at least 3 yr.

Antigens, CD↗

Presentation of proteolipid protein epitopes and B7-1-dependent activation of encephalitogenic T cells by IFN-gamma-activated SJL/J astrocytes.

There is controversy regarding the possible role of glial cells as APCs in the pathogenesis of central nervous system (CNS) demyelinating diseases such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Microglia have been clearly shown to present Ag in the CNS, and due to the proximity of activated astroglial cells to infiltrating T cells and macrophages in demyelinating lesions, it is also possible that astrocytes positively or negatively regulate disease initiation and/or progression. We examined the capacity of IFN-gamma-treated astrocytes from EAE-susceptible SJL/J mice to process and present myelin epitopes. IFN-gamma activation up-regulated ICAM-1, VCAM-1, MHC class II, invariant chain, H2-M, CD40, and B7-1 as determined by FACS and/or RT-PCR analyses. B7-2 expression was only marginally enhanced on SJL/J astrocytes. Consistent with the expression of these accessory molecules, IFN-gamma-treated SJL/J astrocytes induced the B7-1-dependent activation of Th1 lines and lymph node T cells specific for the immunodominant encephalitogenic proteolipid protein (PLP) epitope (PLP139-151) as assessed by proliferation and activation for the adoptive transfer of EAE. Interestingly, IFN-gamma-activated astrocytes efficiently processed and presented PLP139-151, but not the subdominant PLP178-191, PLP56-70, or PLP104-117 epitopes, from intact PLP and a recombinant variant fusion protein of PLP (MP4). The data are consistent with the hypothesis that astrocytes in the proinflammatory CNS environment have the capability of activating CNS-infiltrating encephalitogenic T cells specific for immunodominant epitopes on various myelin proteins that may be involved in either the initial or the relapsing stages of EAE.

Adoptive Transfer↗

T cell selection during the evolution of CD8+ T cell memory in vivo.

Memory T cell responses are frequently highly restricted in terms of receptor usage. How and when such clonotypic dominance is established remains poorly understood. Here we have investigated the evolution of the T cell responses to an epitope from Epstein-Barr virus (EBV), (FLRGRAYGL), by analyzing TCR use of clones specific for this epitope, derived from peripheral blood mononuclear cells taken from individuals early during primary EBV infection and up to 3 years later. We show that, in a given individual, particular T cell clonotypes are selected early during the primary response to this epitope and that the same clonotypes dominate the late memory response. In one individual direct analysis of HLA-B8-restricted FLRGRAYGL-specific T cells, isolated from peripheral blood lymphocytes taken during primary EBV infection using a tetrameric MHC-peptide complex, confirmed the early selection of the dominant clonotypes.

Amino Acid Sequence↗

Arterial embolization for bleeding following hysterectomy for intractable postpartum hemorrhage.

Angiographic embolization is a well documented technique that has been utilized for controlling pelvic hemorrhage. A case is described of a 41-year-old para 3 woman with intractable bleeding following a cesarean hysterectomy for postpartum hemorrhage due to uterine atony and coagulopathy. On angiogram, no bleeding was seen from the uterine vessels. An injection of dye above the origin of the gonadal vessels showed persistent hemorrhage from the left ovarian artery. This report illustrates the importance of intensive resuscitation and supportive measures, and the value of angiographic embolization after failed surgery. It also emphasizes the need to locate the exact bleeding vessel on angiography for embolization to be successful.

Adult↗

Role of corticotropin-releasing factor and substance P in pressor responses of nuclei controlling emotion and stress.

The wide distribution of corticotropin-releasing factor (CRF) and substance P (SP)-immunoreactive cell bodies, nerve terminals and corresponding receptors in pressor nuclei controlling emotion and stress implies that CRF and SP may play important roles in pressor responses of these nuclei; hence CRF or SP was microinjected into these nuclei respectively in Wistar male rats anesthetized with urethane to test this possibility. Microinjection of CRF into nucleus amygdaloideus centralis, nucleus paraventricularis, nucleus ventromedialis, lateral hypothalamus-perifornical region, periaqueductal gray matter, nucleus parabrachialis, locus coeruleus or rostral ventrolateral medulla respectively could evoke pressor responses (but CRF injection into nucleus dorsomedialis could not elicit significant pressor responses). Injection of substance P into all the above nuclei could also elicit hypertensive responses of different magnitudes, whereas normal saline injection into these nuclei had no effect. These results indicate that both CRF and SP in the above mentioned nuclei may play important roles in hypertension induced by prolonged emotional stress.

Animals↗

PAK kinases are directly coupled to the PIX family of nucleotide exchange factors.

The PAK family of kinases are regulated through interaction with the small GTPases Cdc42 and Rac1, but little is known of the signaling components immediately upstream or downstream of these proteins. We have purified and cloned a new class of Rho-p21 guanine nucleotide exchange factor binding tightly through its N-terminal SH3 domain to a conserved proline-rich PAK sequence with a Kd of 24 nM. This PAK-interacting exchange factor (PIX), which is widely expressed and enriched in Cdc42- and Rac1-driven focal complexes, is required for PAK recruitment to these sites. PIX can induce membrane ruffling, with an associated activation of Rac1. Our results suggest a role for PIX in Cdc42-to-Rac1 signaling, involving the PIX/PAK complex.

3T3 Cells↗

Visceral perceptions and gastric myoelectrical activity in healthy women and in patients with bulimia nervosa.

UNLABELLED: Bulimia nervosa remains a common eating disorder in young women. Little is known about upper gastrointestinal symptoms or gastric motility in patients with bulimia nervosa. The aim of this study was to measure gastric myoelectrical activity and hunger/satiety and stomach emptiness/fullness before and after a non-nutrient water load and solid-phase gastric emptying in hospitalized patients with bulimia nervosa (n = 12) and in healthy women (n = 13). Gastric myoelectrical activity was measured by means of cutaneous electrodes; visual analogue scales were used to measure perceptions of hunger/satiety and stomach emptiness/fullness. Before and after a standard water load the bulimia patients reported significantly greater stomach fullness and satiety compared with control subjects (P < 0.01). The percentage of gastric myoelectrical power in the normal 3 cpm range was significantly less in bulimics compared with controls. Power in the 1-2 cpm bradygastria range was significantly greater in bulimia patients before and after the water load compared with the control subjects (P < 0.05). Solid-phase gastric emptying studies using radio-isotope-labelled scrambled eggs showed the lag phase was shortened in the bulimic patients (16 +/- 4 min vs 31 +/- 4 min in controls, P < 0.01), but the percentage of meal emptied at 2 h was similar to control values. IN CONCLUSION: bulimia patients had exaggerated perceptions of stomach fullness and satiety in response to water; and abnormal gastric myoelectrical activity and accelerated lag phase of gastric emptying were objective stomach abnormalities detected in hospitalized patients with bulimia nervosa.

Adolescent↗

Preventing NIDDM among aboriginal people: is exercise the answer? Description of a pilot project using exercise to prevent gestational diabetes.

Rates of diabetes and its complications have reached epidemic proportions among North American Aboriginal peoples. This appears largely due to changes in diet and activity levels associated with a shift away from traditional lifestyles. Since exercise has been shown to be effective in preventing non-insulin-dependent diabetes mellitus (NIDDM), Aboriginal communities may be able to reduce their rates of the disease by incorporating exercise programs into their public health programs. We describe a pilot project in Saskatoon, Saskatchewan, whose ultimate purpose is to evaluate the effect of exercise in preventing gestational diabetes. If successful, this would reduce the risk of developing NIDDM for both women and their offspring.

Adolescent↗

[The rescue of iodine allergy by contrast enhanced CT].

We summarized 51 cases of iodine allergy and allergic shock induced by contract-enhanced computed tomography (CT). It is suggested that (1) the appropriate measures must be taken to prevent the side effects of ionic contrast medium; (2) a set of first-aid drug and essential equipment must be prepared; (3) the staff of CT room must be trained with the first-aid techniques and knowledge.

Adolescent↗

[Determination of tranilast in human plasma by reversed-phase high performance liquid chromatography and its pharmacokinetics].

A simple and rapid method for the determination of tranilast in human plasma by RP-HPLC is described. The analytical column was packed with YWG-C18. The mobile phase consisted of methanol-0.02 mol/L KH2PO4(60:40, V/V; pH 4.2), and detected by UV detector at a wavelength of 333 nm. The plasma sample was injected directly into the HPLC system after precipitation of the protein with methanol. The calibration curve was linear within the concentration range of 0.625-40 mg/L. The average recovery was 100.0% +/- 4.1%, and minimum detectable concentration was 0.2 mg/L. By using this method, the pharmacokinetics of tranilast in the plasma of ten healthy volunteers after oral administration of 200 mg drug were studied. The plasma drug concentration-time curve of volunteers conforms to one-compartment open model.

Anti-Allergic Agents↗

Non-diabetic end-stage renal disease among Saskatchewan aboriginal people.

OBJECTIVE: To determine the rates, causes and outcomes of non-diabetic end-stage renal disease (ESRD) among aboriginal and non-aboriginal people in Saskatchewan. DESIGN: Retrospective population-based study using data from the Canadian Organ Replacement Register. SETTING: Saskatchewan. SUBJECTS: All patients with non-diabetic ESRD diagnosed between Jan. 1, 1981, and Dec. 31, 1990. MAIN OUTCOME MEASURES: Age- and sex-specific as well as age-adjusted incidence rates of non-diabetic ESRD among aboriginal and non-aboriginal people in Saskatchewan, causes of non-diabetic ESRD, mortality rates, causes of death and renal transplantation rates. RESULTS: The 10-year incidence rates of non-diabetic ESRD were higher in all age groups among aboriginal people than among non-aboriginal people. The overall risk ratio for aboriginal people was 2.56. Aboriginal people experienced non-diabetic ESRD at an earlier age and were twice as likely to have a form of glomerulonephritis as a cause. Crude mortality rates, causes of death and transplantation rates were similar in the 2 populations, although we were unable to adjust these for differences in age. CONCLUSION: Although diabetes is the most common cause of ESRD among aboriginal people in Saskatchewan, this population also experiences an excessive burden of non-diabetic ESRD, which is largely explained by a higher rate of glomerulonephritis.

Age Factors↗

Alboaggregins A and B. Structure and interaction with human platelets.

Viper venoms contain a variety of platelet binding proteins including those which bind to platelet GPIb/GPIX. Most of these proteins inhibit von Willebrand factor mediated platelet agglutination. Here we report the primary structures of unique members of this family, alboaggregins A and B, isolated from Trimeresurus albolabris, which have the ability to stimulate platelet agglutination and aggregation. Four chains of alboaggregin A and two chains of alboaggregin B share a high degree of homology and all cysteines in both alboaggregins are conserved. Both alboaggregins caused similar agglutination of fixed platelets. Alboaggregin A induced platelet aggregation and release reaction with EC50 = 10 and 30 nM, respectively, which is 20-fold lower than those for alboaggregin B. These observations suggest that the dimeric structure of alboaggregin B is sufficient to mediate its binding to GPIb and induce agglutination of platelets whereas aggregation and release reaction are significantly enhanced by tetrameric structure of alboaggregin A.

Amino Acid Sequence↗

An improved assembly assay for peptide binding to HLA-B*2705 and H-2K(k) class I MHC molecules.

The assembly assay for peptide binding to class I major histocompatibility complex (MHC) is based on the ability to stabilise MHC class I molecules from mutant cell lines by the addition of suitable peptides. Such cell lines lack a functional transporter associated with antigen presentation (TAP) and as a result accumulate empty, unstable class I molecules in the ER. These dissociate rapidly in cell lysates unless they are stabilised by the addition of an appropriate binding peptide during lysis. The extent of stabilisation of class I molecules is directly related to the binding affinity of the added peptide. However, some MHC class I molecules, including HLA-B * 2705 and H-2Kk are unusually stable in their peptide-receptive state making them inappropriate for analysis using this assay or assays which depend on the ability of peptides to stabilise MHC class I molecules at the cell surface. Here we present an improved method that permits reliable measurements of peptide binding to such class I MHC molecules that are unusually stable in the absence of peptide. Cells are lysed in the presence of peptide and incubated at 4 degrees C. After 2 h, during which peptide binding to empty MHC molecules occurs, the lysate is heated to a temperature which preferentially destabilises those MHC molecules that remain empty. We have used this technique to assay peptide binding to HLA-B * 2705, as well as to the murine allele H-2Kk which also displays a stable phenotype when transfected into TAP-deficient T2 cells and show that this method represents a marked improvement over previous methods in terms of lower background signal and higher recovery of peptide bound molecules.

Amino Acid Sequence↗