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Biomedical subjects

T Truong

Publications and source records attributed to T Truong.

At least 19 recordsLinked to original sources
PubMed2003

Wnt ligand expression in malignant melanoma: pilot study indicating correlation with histopathological features.

AIMS: Secreted Wnt ligands are key proteins regulating cell-cell interactions and cell growth and differentiation. These proteins, along with other components of the Wnt signalling pathway, are involved in the malignant transformation of various human cancers, including malignant melanoma. This study defines the expression of several members of the Wnt ligand family and correlates their expression with histological characteristics. METHODS: The expression of Wnt2, Wnt5a, Wnt5b, Wnt7b, and Wnt10b was defined by in situ, antisense RNA hybridisation of paraffin wax embedded sections of benign naevi and malignant melanoma. Immunoperoxidase based antibody staining was used to define the expression of frizzled (Fz) receptors. RESULTS: All naevi tested strongly expressed Wnt2, Wnt5a, Wnt7b, and Wnt10b. Melanomas characterised by small, uniform cells expressed each of the Wnts in a pattern similar to that seen for benign naevi. In contrast, melanomas characterised by large, pleomorphic cells expressed Wnt10b but did not express Wnt2 and had low levels of expression of Wnt5a. Expression of Wnt7b was variable in these melanomas. Fz receptor expression was present at a low level in normal epithelium and all naevi and melanomas. CONCLUSIONS: The expression pattern of Wnt ligands in malignant melanoma correlates with histopathological features and may provide a basis for the molecular classification of this disease.

Biomarkers, Tumor↗
PubMed2002

Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma.

AIMS: Signalling through the Wnt pathway is integrally associated with colon carcinogenesis. Although activating mutations in the genes for adenomatous polyposis coli (APC) and beta-catenin are clearly associated with colon cancer, less is understood about the role of the upstream secreted ligands (Wnts) and their receptors (frizzled, Fz) in this process. In other systems, increased Wnt signalling has been shown to alter the expression of components of this pathway. This study was designed to test the hypothesis that colon cancer is characterised by aberrant expression of specific Wnt genes and Fz receptors. METHODS: The expression of Wnt genes was assessed by in situ, antisense RNA hybridisation in paraffin wax embedded samples of normal and malignant human colon tissues with probes specific for the individual Wnt genes. The expression of Fz1 and Fz2 was determined by immunoperoxidase based antibody staining on human tissues. RESULTS: Changes in the expression of some ligands and receptors were seen in colon cancer. For example, Wnt2 mRNA was detected in colon cancer but was undetectable in normal colonic mucosa. Differential expression of Wnt5a in normal mucosa was also noted, with increased expression at the base of the crypts compared with the luminal villi and slightly increased expression in colon cancer. Wnt7a exhibited minimal expression in both normal and malignant colon tissues, whereas other Wnt ligands including Wnts 1, 4, 5b, 6, 7b, and 10b were expressed equally and strongly in both normal and malignant colon tissues. In defining cellular responses and phenotype, the type and distribution of Fz receptors may be as important as the pattern of Wnt ligand expression. No expression of Fz receptor 1 and 2 was seen in normal colonic mucosa and in well differentiated tumours. However, poorly differentiated tumours exhibited a high degree of Fz receptor expression, especially at the margin of cellular invasion. CONCLUSIONS: These data indicate that the expression of members of the Wnt signal transduction pathway, distinct from APC and beta-catenin, is integrally associated with the process of colon carcinogenesis. Wnt2, and possibly Wnt5a, may be involved in the progression from normal mucosa to cancer and the expression of Fz1/2 receptors may be involved in processes associated with tumour invasion. Altered expression of these Wnts and Fz receptors may prove useful as prognostic or diagnostic markers for patients with colon cancer.

Biomarkers, Tumor↗
PubMed2001

Germ cell specific promoter drives ectopic transgene expression during embryogenesis.

In this study, we used the male germ cell-specific phosphoglycerate kinase 2 (Pgk2) promoter to generate Pgk2Cre transgenic mice to allow investigation of genes critically involved in meiosis. The Pgk2 promoter had been used previously to target transgene expression to spermatocytes and spermatids in several laboratories including ours. In several Cre targeting experiments using other promoters, ectopic Cre expression had been observed, but the timing and extent of this expression was not analyzed. We demonstrate that in adult mice the Pgk2Cre transgene is expressed specifically in spermatocytes and spermatids, as expected. However, in offspring from matings of Pgk2Cre mice and an H19loxP indicator strain, we discovered that recombination events had occurred in several, but not all, tissues to varying extents. The lacZ-loxP transgenic indicator strain was next used to uncover ectopic Cre expression even in single cells, which indicated that the Pgk2Cre transgene is expressed between days 11 and 15 during embryogenesis in several tissues and organs. Using an RT PCR assay we were unable to detect endogenous Pgk2 mRNA during embryogenesis or in adult tissues other than testis. In conclusion, the Pgk2 promoter is a valid choice for targeting gene expression to meiotic male germ cells, since transient ectopic expression is unlikely to have a discernable effect in most studies, but it may be inappropriate for utilization with Cre recombinase.

Animals↗
PubMed2001

Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer.

Constitutive activation of the Wnt signaling pathway is a root cause of many colon cancers. Activation of this pathway is caused by genetic mutations that stabilize the beta-catenin protein, allowing it to accumulate in the nucleus and form complexes with any member of the lymphoid enhancer factor (LEF1) and T-cell factor (TCF1, TCF3, TCF4) family of transcription factors (referred to collectively as LEF/TCFs) to activate transcription of target genes. Target genes such as MYC, CCND1, MMP7 and TCF7 (refs. 5-9) are normally expressed in colon tissue, so it has been proposed that abnormal expression levels or patterns imposed by beta-catenin/TCF complexes have a role in tumor progression. We report here that LEF1 is a new type of target gene ectopically activated in colon cancer. The pattern of this ectopic expression is unusual because it derives from selective activation of a promoter for a full-length LEF1 isoform that binds beta-catenin, but not a second, intronic promoter that drives expression of a dominant-negative isoform. beta-catenin/TCF complexes can activate the promoter for full-length LEF1, indicating that in cancer high levels of these complexes misregulate transcription to favor a positive feedback loop for Wnt signaling by inducing selective expression of full-length, beta-catenin-sensitive forms of LEF/TCFs.

Colonic Neoplasms↗
PubMed2001

Anesthetic properties of 4-iodopropofol: implications for mechanisms of anesthesia.

BACKGROUND: Positive modulation of gamma-aminobutyric acid type A (GABAA) receptor function is recognized as an important component of the central nervous system depressant effects of many general anesthetics, including propofol. The role for GABAA receptors as an essential site in the anesthetic actions of propofol was recently challenged by a report that the propofol analog 4-iodopropofol (4-iodo-2,6-diisopropylphenol) potentiated and directly activated GABAA receptors, yet was devoid of sedative-anesthetic effects in rats after intraperitoneal injection. Given the important implications of these findings for theories of anesthesia, the authors compared the effects of 4-iodopropofol with those of propofol using established in vivo and in vitro assays of both GABAA receptor-dependent and -independent anesthetic actions. METHODS: The effects of propofol and 4-iodopropofol were analyzed on heterologously expressed recombinant human GABAA alpha1beta2gamma2 receptors, evoked population spike amplitudes in rat hippocampal slices, and glutamate release from rat cerebrocortical synaptosomes in vitro. Anesthetic potency was determined by loss of righting reflex in Xenopus laevis tadpoles, in mice after intraperitoneal injection, and in rats after intravenous injection. RESULTS: Like propofol, 4-iodopropofol enhanced GABA-induced currents in recombinant GABAA receptors, inhibited synaptic transmission in rat hippocampal slices, and inhibited sodium channel-mediated glutamate release from synaptosomes, but with reduced potency. After intraperitoneal injection, 4-iodopropofol did not produce anesthesia in mice, but it was not detected in serum or brain. However, 4-iodopropofol did produce anesthesia in tadpoles (EC50 = 2.5 +/- 0.5 microM) and in rats after intravenous injection (ED50 = 49 +/- 6.2 mg/kg). CONCLUSIONS: Propofol and 4-iodopropofol produced similar actions on several previously identified cellular and molecular targets of general anesthetic action, and both compounds induced anesthesia in tadpoles and rats. The failure of 4-iodopropofol to induce anesthesia in rodents after intraperitoneal injection is attributed to a pharmacokinetic difference from propofol rather than to major pharmacodynamic differences.

Anesthetics, Intravenous↗
PubMed2000

Provocative discography in patients after limited lumbar discectomy: A controlled, randomized study of pain response in symptomatic and asymptomatic subjects.

STUDY DESIGN: This was a prospective observational study of patients with low back pain and those without after laminotomy and discectomy. OBJECTIVES: To determine, using a strict experimental design, the relative pain intensity response to provocative discography in symptomatic and asymptomatic subjects after lumbar discectomy for intervertebral disc herniation. BACKGROUND: Provocative discography frequently is used to evaluate persistent or recurrent low back pain syndromes in patients who have undergone posterior discectomy. The validity of interpreting painful injections during this procedure has not been critically assessed. The prevalence of significantly painful disc injections in a group with good outcomes after surgery is not known. Knowing the rates of significantly painful injections in asymptomatic patients after lumbar discectomy may clarify the meaning of painful injections in symptomatic patients. METHODS: From a cohort of 240 patients who had undergone single-level limited discectomy for sciatica, 20 asymptomatic volunteers were recruited for experimental three-level lumbar discography. Inclusion criteria required nearly perfect scores on standardized back pain rating instruments, no other spinal pathology, and normal psychometric screening. A control group of 27 symptomatic patients, after single-level discectomy with intractable low back pain syndrome, and without other spinal pathology, underwent discography. Seven patients in the control group had normal psychometric tests. Experienced raters who were blinded to control versus experimental status of the subjects scored the magnetic resonance imaging, discogram, psychometric tests, and discography videotapes of the subjects' pain behavior. RESULTS: There were 8 of 20 (40%) positive injections of discs that had previous surgery in the asymptomatic group and 17 of 27 (63%) positive injections in the symptomatic group. Specifically with regard to the symptomatic group, there were 3 of 7 (43%) positive injections (all concordant) in patients with normal psychometric scores, as compared with 14 of 20 (70%) positive injections (12 concordant) in patients with abnormal psychometric scores. Injections of discs that had previous surgery resulted in a mean pain score of 2.1 of 5 in the asymptomatic group, 2.1 in the symptomatic group with normal psychometric scores, and 3.4 in the symptomatic group with abnormal psychometric scores. Of the discs not treated with surgery, 2 were positive in the asymptomatic group (10%), 3 in 2 symptomatic subjects with normal psychological testing (29), and 18 in 13 symptomatic subjects with abnormal psychometric testing (76%). CONCLUSIONS: A high percentage of asymptomatic patients with normal psychometric testing who previously have undergone lumbar discectomy will have significant pain on injection of their discs that had previous surgery (40%). This is not significantly different from the experience of symptomatic patients with normal psychometric testing undergoing discography on discs that had previous surgery. Patients with abnormal psychological profiles have significantly higher rates of positive disc injections than either asymptomatic volunteers or symptomatic subjects with normal psychological screening.

Adult↗
PubMed2000

The rates of false-positive lumbar discography in select patients without low back symptoms.

STUDY DESIGN: Experimental disc injections in subjects with no history of low back symptoms. OBJECTIVE: To determine in an experimental setting the relative pain response and pain-related behavior in selected subjects without a history of low back pain undergoing lumbar discography. This study aimed to select a study population that more closely represented patients undergoing discography in clinical practice. SUMMARY OF BACKGROUND DATA: Previous work has shown that in young, healthy men with little degenerative disc disease and no history of low back problems, discographic injections usually did not cause significant pain. This group differed from the patients who usually undergo discographic evaluation in clinical practice. Most clinical patients are older, have significant degenerative disc disease, have behavioral changes associated with chronic pain, and often have confounding psychosocial troubles. The authors undertook to study discography in subjects without low back pain but with clinical profiles similar to patients undergoing discography in clinical practice. METHODS: Twenty-six individuals, mean age 43 years, with no history of low back pain had lumber discography according to the strict protocol of Walsh et al. Of these, 10 were pain-free; 10 had chronic neck and arm pain, but no low back symptoms; and 6 had primary somatization disorders without low back symptoms.- RESULTS: Significant positive pain response and pain-related behavior with discography were found in 10% of the pain-free group, in 40% of the chronic cervical pain group, and in 83% of the somatization disorder group completing the injections. Twenty-four subjects had negative control discs. Discs with annular disruption were more likely to be painful on injection, particularly in those individuals with ongoing compensation issues, chronic pain, or abnormal psychological testing.- CONCLUSION: If strict criteria are applied, the rate of false-positive discography may be low in subjects with normal psychometric profiles and without chronic pain. Significantly painful injections were very common in subjects with annular disruption and chronic pain or abnormal psychometric testing.

Adult↗
PubMed2000

Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade.

We have previously shown that antibodies to CTLA-4, an inhibitory receptor on T cells, can be effective at inducing regression of transplantable murine tumors. In this study, we demonstrate that an effective immune response against primary prostate tumors in transgenic (TRAMP) mice can be elicited using a strategy that combines CTLA-4 blockade and an irradiated tumor cell vaccine. Treatment of TRAMP mice at 14 weeks of age resulted in a significant reduction in tumor incidence (15% versus control, 75%), as assessed 2 months after treatment. Histopathological analysis revealed that treated mice had a lower tumor grade with significant accumulation of inflammatory cells in interductal spaces when treated with anti-CTLA-4 and a granulocyte-macrophage colony-stimulating factor-expressing vaccine. Vaccination of nontransgenic mice with this regimen resulted in marked prostatitis accompanied by destruction of epithelium, indicating that the immune response was, at least in part, directed against normal prostate antigens. These findings demonstrate that this combinatorial treatment can elicit a potent antiprostate response and suggest potential of this approach for treatment of prostate cancer.

Abatacept↗
PubMed2000

Immunohistochemistry and microwave decalcification of human temporal bones.

Processing of human temporal bones is a long, expensive process and the resulting celloidin sections are difficult to use for immunohistochemistry. We tested the ability of immunohistochemical assays to work in human temporal bones that were decalcified using a microwave oven. Tissue was trimmed to an approximate cube (1.5-2 cm/side) containing only the cochlea and immersed in fresh EDTA with paraformaldehyde every 6 h. This sized block required 190-400 h to decalcify. The decalcified tissue was embedded in paraffin and sectioned. Sections were immunoassayed with anti-cytochrome c oxidase, anti-neurofilament or anti-peripherin. All three antibodies labeled the appropriate structures. This procedure may stimulate advancement in the understanding of human inner ear pathology.

Calcium↗
PubMed2000

Estimation of the amyotrophic lateral sclerosis incidence by capture-recapture method in the Limousin region of France.

Amyotrophic lateral sclerosis (ALS) is a rapidly fatal degenerative neurological disease categorized among motor neuron diseases. In the literature, the incidence of ALS varies between 0.7 and 2.4 per 100, 000 inhabitants. A study using the capture-recapture method (multiple records system analysis) was undertaken in Limousin (France) ascertaining all patients having onset of definite or probable ALS during the period 1994-1995. Three information sources able to identify these new ALS cases were selected: the first source was a computerized database of the Neurology Department of the University Hospital of Limoges; the second source consisted of the neurologists of the Limousin region and neighboring provinces (county-sized regions); the third source grouped the hospitals of the Limousin region and neighboring provinces (county-sized regions). During this period, 46 new cases of ALS were seen, corresponding to an observed mean annual incidence of 3.2 (+/-0.6) per 100,000 inhabitants. After standardization for age, the annual incidence was 2.5 per 100,000 inhabitants. The number of new cases estimated by the capture-recapture method was 70, corresponding to an estimated mean annual incidence of 4.9 (+/-1.0) for 100,000 inhabitants. Hence, statistical modeling utilizing partially overlapping information sources permitted a more exhaustive compendium of the new cases of ALS and may be a truer reflection of actual disease incidence than has been previously reported.

Amyotrophic Lateral Sclerosis↗
PubMed1999

False-positive findings on lumbar discography. Reliability of subjective concordance assessment during provocative disc injection.

STUDY DESIGN: Experimental disc injections in subjects with no history of low back symptoms. OBJECTIVE: To determine in an experimental model the reliability of patients' subjective interpretation of pain concordancy during provocative disc injection. BACKGROUND: Discography in the evaluation of low back pain relies on a patient's subjective assessment of pain magnitude and quality during disc injection. Reproduction of significant pain on disc injection, which is similar to patients' usual pain, is believed to prove that the disc injected is the source of the patient's low back pain. In the current study, this hypothesis was tested in a controlled setting on patients with known nonspinal pain in a common referral area of discogenic pain. METHODS: Patients with no history of low back pain were recruited to participate in a study of discography. Patients scheduled to undergo posterior iliac crest bone graft harvesting for nonthoracolumbar procedures were evaluated with lumbar radiography, magnetic resonance imaging, and psychometric testing. Two to 4 months after bone graft harvesting, patients underwent lumbar discography by strict blinded protocol. Patients were asked to compare the sensations elicited at discography to their usual back/buttock pain since bone graft harvesting. Pain was rated as 0-5 on a pain thermometer and concordancy was rated as none, dissimilar, similar, or exact. RESULTS: Eight subjects completed the study, and 24 discs were injected. Of the 14 disc injections causing some pain response, 5 were believed to be "different" (nonconcordant) pains (35.7%); 7 were "similar" (50.0%), and 2 were "exact" pain reproductions (14.3%). The presence of anular disruption predicted concordant pain reproduction (P < 0.05). Of 10 discs with anular tears, injection of 5 elicited pain that was similar to or an exact reproduction of pain at the iliac crest bone graft harvest sites. By the usual criteria for positive discography, 4 of the 8 patients (50%) would have been classified as positive. In these patients, the pain on a single disc injection was very painful, and the pain quality was noted to be exact or similar to the usual discomfort. All subjects had a negative control disc. CONCLUSIONS: The findings of this study demonstrate that patients with no history of low back pain who had undergone posterior iliac bone graft harvesting for nonlumbar procedures often experienced a concordant painful sensation on lumbar discography with their usual gluteal area pain. Thus, the ability of a patient to separate spinal from nonspinal sources of pain on discography is questioned, and a response of concordant pain on discography may be less meaningful than often assumed.

Adult↗
PubMed1998

Integrin and cadherin synergy regulates contact inhibition of migration and motile activity.

Integrin receptors play a central role in cell migration through their roles as adhesive receptors for both other cells and extracellular matrix components. In this study, we demonstrate that integrin and cadherin receptors coordinately regulate contact-mediated inhibition of cell migration. In addition to promoting proliferation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and A. Horwitz. 1996. J. Cell Biol. 133:169-184), ectopic expression of the alpha5 integrin in cultures of primary quail myoblasts promotes a striking contact-mediated inhibition of cell migration. Myoblasts ectopically expressing alpha5 integrin (alpha5 myoblasts) move normally when not in contact, but upon contact, they show inhibition of migration and motile activity (i.e., extension and retraction of membrane protrusions). As a consequence, these cells tend to grow in aggregates and do not migrate to close a wound. This phenotype is also seen with ectopic expression of beta1 integrin, paxillin, or activated FAK (CD2 FAK) and therefore appears to result from enhanced integrin-mediated signaling. The contact inhibition observed in the alpha5 myoblasts is mediated by N-cadherin, whose expression is upregulated more than fivefold. Perturbation studies using low calcium conditions, antibody inhibition, and ectopic expression of wild-type and mutant N-cadherins all implicate N-cadherin in the contact inhibition of migration. Ectopic expression of N-cadherin also produces cells that show inhibited migration upon contact; however, they do not show suppressed motile activity, suggesting that integrins and cadherins coordinately regulate motile activity. These observations have potential importance to normal and pathologic processes during embryonic development and tumor metastasis.

Animals↗
PubMed1998

Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells.

Negative as well as positive co-stimulation appears to play an important role in controlling T cell activation. CTLA-4 has been proposed to negatively regulate T cell responses. CTLA-4-deficient mice develop a lymphoproliferative disorder, initiated by the activation and expansion of CD4+ T cells. To assess the function of CTLA-4 on CD8+ T cells, CTLA-4(-/-) animals were crossed to an MHC class I-restricted 2C TCR transgenic mouse line. We demonstrate that although the primary T cell responses were similar, the CTLA-4-deficient 2C TCR+ CD8+ T cells displayed a greater proliferative response upon secondary stimulation than the 2C TCR+ CD8+ T cells from CTLA-4 wild-type mice. These results suggest that CTLA-4 regulates antigen-specific memory CD8+ T cell responses.

Abatacept↗
PubMed1998

[Lead intoxication and amyotrophic lateral sclerosis].

A seventy-six-year-old patient developed a bulbar form of amyotrophic lateral sclerosis, after chronic lead intoxication from drinking water. Treatment with 2,3 dimercaptosuccinic acid was administered for six months and had no effect on clinical course. We discuss the imputability of lead as a possible etiological factor.

Aged↗
PubMed1997

Thymocyte development is normal in CTLA-4-deficient mice.

Recent studies indicate that CTLA-4 interaction with B7 ligands transduces an inhibitory signal to T lymphocytes. Mice homozygous for a null mutation in CTLA-4 have provided the most dramatic example of the functional importance of CTLA-4 in vivo. These animals develop a fatal lymphoproliferative disorder and were reported to have an increase in CD4(+) and CD8(+) thymocytes and CD4(-)CD8(-) thymocytes, and a decrease in CD4(+)CD8(+) thymocytes. Based on these observations, it was proposed that CTLA-4 is necessary for normal thymocyte development. In this study, CTLA-4-deficient mice carrying an insertional mutation into exon 3 of the ctla-4 gene were generated. Although these mice display a lymphoproliferative disorder similar to previous reports, there was no alteration in the thymocyte profiles when the parathymic lymph nodes were excluded from the thymi. Further, thymocyte development was normal throughout ontogeny and in neonates, and there was no increase in thymocyte production. Finally, T cell antigen receptor signaling, as assessed by proximal and distal events, was not altered in thymocytes from CTLA-4(-/-) animals. Collectively, these results clearly demonstrate that the abnormal T cell expansion in the CTLA-4-deficient mice is not due to altered thymocyte development and suggest that the apparent altered thymic phenotype previously described was due to the inclusion of parathymic lymph nodes and, in visibly ill animals, to the infiltration of the thymus by activated peripheral T cells. Thus it appears that CTLA-4 is primarily involved in the regulation of peripheral T cell activation.

Abatacept↗
PubMed1996

Ectopic ureter with complete ureteric duplication: conservative surgical management.

To assess the outcome of conservative procedures, the authors reviewed their experience in the management of 31 ectopic ureters with complete ureteric duplication. Twenty-eight girls and three boys (aged 19 days to 10 years; mean, 30 months) were operated on between 1968 and 1994. Twenty-four of the children presented for evaluation of dribbling urinary incontinence and/or febrile urinary tract infections; seven presented after prenatal ultrasonographic diagnosis of hydronephrosis. The location of the ectopic orifice was identified in 25 children: bladder neck (6), posterior urethra (6), vagina (7), and vestibule (6). Upper pole nephroureterectomy was performed in 16 children who had nonfunctioning renal segments. Ureterovesical reimplantation was performed in 10 children who had functioning segments. In five borderline cases, temporary cutaneous ureterostomy was performed, followed by ureteropyelostomy (2), ureterovesical reimplantation (2), and upper pole nephrectomy (1). Histological examination of the polar nephrectomy specimens showed lesions of dysplasia in only four cases (24%). The follow-up period ranged from 6 months to 20 years (mean, 66 months). All children who presented with incontinence became continent after polar nephrectomy or conservative surgery. One child required surgical revision of the ureteropyelostomy anastomosis. Of the 12 children who had ureterovesical reimplantation, none needed further procedures. Ectopic ureters in duplex systems with functioning renal segments should be conserved.

Biopsy↗