Biomedical subjects

T Vu

Publications and source records attributed to T Vu.

At least 37 records · Page 2Linked to original sources

PubMed1997

Effect of intramuscular 15-methyl prostaglandin F2 alpha after second-trimester delivery.

OBJECTIVE: To determine whether 15-methyl prostaglandin (PG) F2 alpha shortens the third stage of labor in second-trimester pregnancy loss. METHODS: This was a randomized, double-blind, placebocontrolled study of women between 13 and 28 weeks' gestation admitted for spontaneous or induced pregnancy termination. Subjects were randomized on admission to receive either PG (250 micrograms) or placebo (normal saline), 1 mL intramuscularly every 20 minutes, for a maximum of three doses if the placenta had not delivered spontaneously within 10 minutes of the fetus. A dilute oxytocin infusion was given to women in both groups. The patients were managed expectantly with hourly vaginal examinations until intervention was required or up to 6 hours, when curettage was scheduled. RESULTS: Thirty-eight women received PG and 29 received placebo. There was no difference between the groups with regard to method of pregnancy termination or gestational age. There was a statistically significant decrease in the time from first injection to placental delivery (40.0 versus 92.5 minutes; P = .02) between the PG and control groups, respectively. CONCLUSIONS: The therapeutic use of PG in the third stage of labor in second-trimester pregnancy loss reduces the time to complete spontaneous placental delivery.

Dinoprost↗

PubMed1997

Shortened survival after relapse in T-cell acute lymphoblastic leukemia patients with p16/p15 deletions.

p16 Alterations were detected in > 60% of 103 primary T-ALL samples. In paired diagnosis-relapse patient samples, 80% of the relapse samples with p16 deletion were deleted at diagnosis. When p16 was homozygously deleted, p15 gene alterations were found in 72% of the diagnosis T-ALL patient samples, increasing significantly to 100% at relapse. Alterations of p18 were not detected. No clinical significance of p15/p16 gene deletion in diagnosis T-ALL was found with respect to white blood cell (WBC) count, incidence of mediastinal mass, rate of relapse, duration of first remission or event-free survival. In relapse T-ALL, however, patients with p16 deletion experienced a significantly shorter duration of post-relapse survival, demonstrating that p16 deletion is clinically significant in T-ALL.

Carrier Proteins↗

PubMed1997

Decreased expression of Wilms' tumor gene WT-1 and elevated expression of insulin growth factor-II (IGF-II) and type 1 IGF receptor genes in prostatic stromal cells from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. We have previously documented that the insulin-like growth factor (IGF) axis is critical for prostate cell growth and is abnormal in BPH. The type 1 IGF receptor (IGF-1R) is constitutively expressed by most body tissues and plays a significant role in regulating cell proliferation, consistent with the role of its ligands (IGF-I and IGF-II) as important mitogenic factors. The Wilms' tumor gene product (WT-1) is a tumor suppressor that has been shown to be altered in rare kidney tumors and is known to regulate IGF-II and IGF-1R. We investigated the possibility that the expression of prostatic WT-1, IGF-1R, and IGF-II genes is altered in patients with BPH. We utilized primary cultures of prostatic stromal cells grown from normal (n = 9) and hyperplastic (n = 9) surgical specimens and analyzed WT-1, IGF-1R, and IGF-II messenger RNA levels. In all of the BPH cell strains, WT-1 expression (measured by RT-PCR and RNase protection assays) was strikingly lower than that found in normal strains (0-20% of normal, mean 14% of normal, P < 0.01). The expression of both the IGF-1R (300% of normal, P < 0.05) and IGF-II (1000% of normal, P < 0.01) messenger RNAs was higher in BPH strains as compared with normal strains. No changes were seen in stromal cell strains derived from prostatic adenocarcinoma. Thus, in cultured human prostatic stromal cell strains from patients with BPH, decreased WT-1 gene expression is associated with increases in the expression of the IGF-1R and IGF-II genes that are known transcriptional targets of WT-1. These findings indicate that reduced expression of the WT-1 tumor suppressor gene and elevated IGF-1R and IGF-II gene expression may be involved in the pathophysiology of prostatic hyperplasia, implying a new role for the Wilms' tumor gene in nonmalignant states.

Aged↗

PubMed1996

Frequent deletion in the methylthioadenosine phosphorylase gene in T-cell acute lymphoblastic leukemia: strategies for enzyme-targeted therapy.

Methylthioadenosine phosphorylase (MTAP), an enzyme essential for the salvage of adenine and methionine, is deficient in a variety of cancers, including acute lymphoblastic leukemia (ALL). Because the MTAP gene is located adjacent to the tumor-suppressor gene p16 on chromosome 9p21 and more than 60% of T-cell ALL (T-ALL) patients have deletion in the p16 gene, we examined the status of the MTAP gene in T-ALL patients. Quantitative polymerase chain reaction amplification of exon 8 of MTAP showed a deletion in 16 of 48 (33.3%) patients at diagnosis and in 13 of 33 (39.4%) patients at relapse. Southern blot analysis showed that, in addition to deletion of the entire MTAP gene, a common break point was between exons 4 and 5, resulting in deletion of exons 5 through 8. The finding of frequent deficiency of MTAP in T-ALL offers the possibility of an enzyme targeted therapy for T-ALL. MTAP(-) T-ALL-derived cell line, CEM cells were very sensitive to methionine deprivation, with cell viability at 50% of control as early as 48 hours after methionine deprivation. In contrast, methionine deprivation had little effect on the viability of normal lymphocytes or on their proliferative response to phytohemagglutinin. Alanosine, an inhibitor of AMP synthesis, inhibited the growth of both MTAP(+) (Molt-4 and Molt-16) and MTAP(-) (CEM and HSB2) cell lines. However, the addition of methylthioadenosine, the substrate of MTAP, protected the MTAP(+) cells but not the MTAP(-) cells from alanosine toxicity. These findings suggest the possibility of targeting MTAP for selective therapy of T-ALL.

Adenosine Monophosphate↗

PubMed1996

Chimeric vesicular monoamine transporters identify structural domains that influence substrate affinity and sensitivity to tetrabenazine.

The vesicular monoamine transporters (VMATs) 1 and 2 show close sequence similarity but substantial differences in apparent substrate affinity and drug sensitivity. To identify structural domains that determine these functional characteristics, chimeric transporters were constructed and their properties were analyzed in a heterologous expression system. The results implicate multiple regions in the recognition of serotonin and histamine and the sensitivity to tetrabenazine. Two domains of VMAT2, one extending from transmembrane domain (TMD) 5 to the beginning of TMD8 and the other from the end of TMD9 through TMD12, increase the affinity for serotonin and histamine as well as the sensitivity to tetrabenazine but only in the context of more C-terminal and more N-terminal VMAT2 sequences, respectively. In addition, the extreme N terminus of VMAT2 alone suffices to confer a partial increase in substrate affinity and tetrabenazine sensitivity. Despite these similarities among the interactions with serotonin, histamine, and tetrabenazine, the region of VMAT2 from TMD3 through TMD4 increases serotonin affinity but not histamine affinity or tetrabenazine sensitivity, and whereas the region from TMD5 to TMD8 of VMAT2 increases serotonin affinity in the context of more C-terminal VMAT2 sequences, the region encompassing TMD5 through TMD7 reduces serotonin but not histamine affinity or tetrabenazine sensitivity in the context of more N-terminal VMAT2 sequences. Thus, the chimeric analysis also reveals differences between serotonin recognition and the recognition of both histamine and tetrabenazine that may account for the observed differences in their interaction with the transport protein.

Animals↗

PubMed1996

Parabrachial nucleus projection to the amygdala in the rat: electrophysiological and anatomical observations.

The amygdala, an important limbic forebrain centre, is the recipient of projections from a number of autonomic brainstem nuclei including the pontine parabrachial nucleus. This study examined the influence of electrical stimulation of the parabrachial nucleus on the excitability of amygdala neurons and their response to two cardiovascular stimuli, namely baroreceptor activation and the administration of systemic angiotensin II. We also defined the chemical identity of some amygdala neurons that receive parabrachial nucleus projections by combining the transport of the anterograde tracer Phaseolus vulgaris leucoagglutinin injected into the parabrachial nucleus with immunocytochemical labelling of neurotensin and galanin profiles within the amygdala. In urethane-anesthetized rats, stimulation of parabrachial nucleus evoked four basic types of synaptic responses in amygdala cells: (1) a short duration (< 100 ms) excitation in 75 of 167 neurons, (2) a longer duration (> 100 ms) excitatory response in 36 neurons, (3) an inhibitory response in 32 cells, and (4) more complex responses consisting of excitation-inhibition or inhibition-excitation sequences in the remainder of the cells. Thirty-seven of 72 amygdala neurons activated synaptically by parabrachial nucleus stimulation also responded to baroreceptor activation or intravenous angiotensin II. Anatomical data revealed the presence of Phaseolus vulgaris leucoagglutinin labelled terminals predominantly within the lateral, medial, and capsular subdivisions of the central nucleus of amygdala. Phaseolus vulgaris leucoagglutinin varicosities and boutons were observed apposed to the neurotensin and galanin neuronal perikarya within the central nucleus of amygdala. The electrophysiological results provide a framework whereby parabrachial nucleus efferents influence the activity of amygdala neurons that are responsive to cardiovascular stimuli. Furthermore, the anatomical data indicate that a portion of the parabrachial nucleus input is directed toward galanin and neurotensin neurons within the central nucleus of amygdala.

Amygdala↗

PubMed1996

Aplastic anaemia and paroxysmal nocturnal haemoglobinuria: a study of the GPI-anchored proteins on human platelets.

Twenty-six consecutive patients with acquired aplastic anaemia (AA) and nine patients with de novo paroxysmal nocturnal haemoglobinuria (PNH) were included in this study. In these 35 patients a GPI-anchored molecule defect at the platelet surface was investigated by flow-cytometry. Platelets from eight out of the nine patients with de novo PNH were found to be deficient for the GPI-anchored molecule CD55, CD58 and CD59. We also detected a GPI-anchored molecule defect on monocytes, granulocytes, and erythrocytes in all patients with de novo PNH. Among the 26 AA patients, a GPI defect was detected on platelets in five patients. Interestingly, these five patients were also found to have a GPI-anchored molecule defect on erythrocytes, whereas in 10 patients the GPI-anchored molecule defect was only detected on monocyte and polymorphonuclear (PMN) cells.

Anemia, Aplastic↗

PubMed1996

A novel set of uncoordinated mutants in Caenorhabditis elegans uncovered by cold-sensitive mutations.

A set of uncoordinated (Unc) cold-sensitive (cs) mutants was isolated at a stringent condition of 11 degrees C. About half of the 13 independently isolated cs-Unc mutants were alleles of three X-linked Unc mutants that exhibited the "kinker" phenotype. The remaining four isolates identified new mutants that exhibited "kinker," "coiler," or severe paralytic phenotypes. The temperature-sensitive period (TSP) for each gene was determined. As a homozygous or heterozygous dominant, unc-125 exhibited a TSP throughout all stages of development. Its severe paralysis was immediately observed upon a shift down to 11 degrees C and reversed upon a shift up to 23 degrees C. The reversible thermolability of the unc-125 gene product indicated that it may function in a multicomponent process involved in neuro-excitation.

Alleles↗

PubMed1996

RT-PCR analysis of MMP-9 expression in human articular cartilage chondrocytes and synovial fluid cells.

This report presents a method for analyzing matrix metalloproteinase-9 (92 kD gelatinase) MMP-9 mRNA expression using reverse transcription polymerase chain reaction (RT-PCR). With this method, chondrocytes isolated from small samples of osteoarthritic cartilage showed significantly elevated signal for MMP-9 mRNA compared to normal cartilage. In addition, cells of synovial fluid samples aspirated from osteoarthritic joints also exhibited MMP-9 expression using this technique. RT-PCR proved to be a sensitive method for assessing MMP-9 regulation in osteoarthritic and normal cartilage, and may provide a useful index of arthritic cartilage and synovial fluid cell metabolism when limited tissue is available.

Cartilage, Articular↗

PubMed1995

Aplastic anemia and paroxysmal nocturnal hemoglobinuria: search for a pathogenetic link.

The association of paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA) raises the yet unresolved questions as to whether these two disorders are different forms of the same disease. We compared two groups of patients with respect to cytogenetic features, glycosylphosphatidylinositol (GPI)-linked protein expression, protein C/protein S/thrombomodulin/antithrombin III activity, and PIG-A gene expression. The first group consisted of eight patients with PNH (defined as positive Ham and sucrose tests at diagnosis), and the second, 37 patients with AA. Twelve patients with AA later developed a PNH clone. Monoclonal antibodies used to study GPI-linked protein expression (CD14 [on monocytes], CD16 [on neutrophils], CD48 [on lymphocytes and monocytes], CD67 [on neutrophils and eosinophils], and, more recently, CD55, CD58, and CD59 [on erythrocytes]) were also tested on a cohort of 20 normal subjects and five patients with constitutional AA. Ham and sucrose tests were performed on the same day as flow-cytometric analysis. Six of 12 patients with AA, who secondarily developed a PNH clone, had clinical symptoms, while all eight patients with PNH had pancytopenia and/or thrombosis and/or hemolytic anemia. Cytogenetic features were normal in all but two patients. Proteins C and S, thrombomodulin, and antithrombin III levels were within the normal range in patients with PNH and in those with AA (with or without a PNH clone). In patients with PNH, CD16 and CD67 expression were deficient in 78% to 98% of the cells and CD14 in 76% to 100%. By comparison, a GPI-linked defect was detected in 13 patients with AA, affecting a mean of 32% and 33% of CD16/CD67 and CD14 cell populations, respectively. Two of three tested patients with PNH and 1 of 12 patients with AA had a defect in the CD48 lymphocyte population. In a follow-up study of our patient cohort, we used the GPI-linked molecules on granulocytes and monocytes investigated earlier and added the study of CD55, CD58, and CD59 on erythrocytes. Two patients with PNH and 14 with AA were studied for 6 to 13 months after the initial study. Among patients with AA, four in whom no GPI-anchoring defect was detected in the first study had no defect in follow-up studies of all blood-cell subsets (including erythrocytes). Analysis of granulocytes, monocytes, and erythrocytes was performed in 7 of 13 AA patients in whom affected monocytes and granulocytes were previously detected. A GPI-anchoring defect was detected on erythrocytes in five of six.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1995

Transfection of a murine fibrosarcoma with intercellular adhesion molecule-1 enhances the response to adoptive immunotherapy.

BACKGROUND: Increasing the ability of antitumor effector cells to leave the vasculature and gain access to tumor cells may improve therapeutic efficacy. We undertook this study to determine whether increased expression of intercellular adhesion of molecular-1 (ICAM-1) by gene transfection would result in an improved response to adoptive immunotherapy in vivo. METHODS: C57BL/6 mice received 1 x 10(6) tumor cells on day 0. Tumor cells examined were MCA-105 (parental), NeoR (MCA-105 transfected with the neomycin resistance gene), or Clones 81 or 149 (MCA-105 cotransfected with NeoR and the gene for ICAM-1 and highly express ICAM-1). Animals were treated by use of no treatment, interleukin-2 alone (days 10 through 14), hyperthermia alone (days 10 and 13), or interleukin-2 + hyperthermia, and tumor growth was reported as a ratio to size on day 10. In vitro cytotoxicity was assayed by using murine lymphokine-activated killer cells. RESULTS: Tumors transfected with ICAM-1 and treated with hyperthermia + immunotherapy grew significantly (p < 0.05) slower (mean, 0.78 +/- 0.16 on day 19) than parental tumor (size, 1.35 +/- 0.22) or tumor cells transfected with NeoR alone (1.21 +/- 0.19). Tumors containing both MCA-105 and Clone 81 treated with hyperthermia + immunotherapy grew significantly slower (1.58 +/- 0.49 on day 19, p < 0.05) than untreated Clone 81 (2.38 +/- 0.46) or treated MCA-105 (2.49 +- 0.29) but more rapidly than treated Clone 81 (1.18 +/- 0.08), suggesting a paracrine efect for ICAM-1. CONCLUSIONS: These findings show that increased expression of ICAM-1 by tumor cells results in a significant increase in antitumor efficacy of combined interleukin-2 and hyperthermia in a murine model. Although the mechanism has yet to be elucidated, modulation of cellular adhesion may play a role in the therapeutic efficacy of cellular immunotherapy.

Animals↗

PubMed1994

The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction.

The gene for cytochrome P4501A2 is constitutively expressed in the liver of vertebrates and shows induced expression when an organism is exposed to polycyclic aromatic hydrocarbons and halogenated hydrocarbons. To identify DNA elements regulating transcription of the human CYP1A2 gene, transient transfection experiments were conducted in the human hepatoma cell line HepG2. Dissection of the 5'-flanking portion of the CYP1A2 gene identified two regions that contributed to the overall induction by 3-methylcholanthrene. One region located at -2532/-2423 contains an xenobiotic-responsive element-like sequence, termed X1, that binds a nuclear 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible protein in HepG2 and wild type mouse Hepa-1 cells, but not in the Ah receptor nuclear translocation defective mouse C- mutant c4 cells. In addition, deletion of this region of the CYP1A2 gene reduces the 3-methylcholanthrene (3-MC)-initiated induction of chloramphenicol acetyltransferase activity in both promoter- and enhancer-specific constructs. The second responsive region is located at -2259/-1987. This region of the gene contains a second xenobiotic-responsive element-like element, but this element does not associate with the nuclear Ah receptor. However, there does exist several potential AP1 binding sites and a conserved TATA box. A DNA fragment from -2259/-1970 that contains these elements was shown to function as an efficient eukaryotic promoter, in addition to supporting 3-MC-induced promoter activity. These results suggest that Ah receptor-specific and promoter-specific elements regulate the expression of the human CYP1A2 gene.

Animals↗

PubMed1994

D-dimer levels in the cerebrospinal fluid: a marker of central nervous system involvement in neoplastic disease.

D-dimer assay was performed on 145 cerebrospinal fluid (CSF) samples from patients with or without neoplastic diseases. Levels of D-dimers were significantly higher in carcinoma and lymphoid malignancies with clinical or biological evidence of central nervous system (CNS) involvement than in diseases without such complications. In one patient, serial determinations of D-dimers were well correlated with the appearance and disappearance of CNS involvement. Although this test is not specific for neoplastic affections, our data suggest that the measurement of D-dimers in CSF may be useful in the diagnosis of CNS involvement of neoplastic cells and in monitoring intrathecal therapy in patients with lymphoma, acute lymphoblastic leukaemia or carcinoma. In this study, the D-dimer assay was also positive in some non neoplastic diseases, but failed to differentiate subarachnoid haemorrhage from traumatic lumbar puncture.

Adult↗

PubMed1993

Endotoxin-induced tissue factor in human monocytes is dependent upon protein kinase C activation.

Tissue factor (TF) is a transmembrane receptor which, in association with factors VII and VIIa, activates factor IX and X, thereby activating the coagulation protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes transcribe, synthesize and express TF on their surface. We investigated whether LPS-induced TF in human monocytes is mediated by protein kinase C (PKC) activation. The PKC agonists phorbol 12-myristate 13-acetate (PMA) and phorbol 12, 13 dibutyrate (PdBu) were both potent inducers of TF in human monocytes, whereas 4 alpha-12, 13 didecanoate (4 alpha-Pdd) had no such effect. Both LPS- and PMA-induced TF activity were inhibited, in a concentration dependent manner, by three different PKC inhibitors: H7, staurosporine and calphostin C. TF antigen determination confirmed that LPS-induced cell-surface TF protein levels decreased in parallel to TF functional activity under staurosporine treatment. Moreover, Northern blot analysis of total RNA from LPS- or PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to H7 and staurosporine. The decay rate of LPS-induced TF mRNA evaluated after the arrest of transcription by actinomycin D was not affected by the addition of staurosporine, suggesting that its inhibitory effect occurred at a transcriptional level. We conclude that LPS-induced production of TF and its mRNA by human monocytes are dependent on PKC activation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

Interleukin-10 inhibits endotoxin-induced tissue factor mRNA production by human monocytes.

In Gram-negative septic shock, human monocytes synthesize and express on their cytoplasmic membrane tissue factor (TF), a potent activator of the coagulation cascades. The role of TF in triggering disseminated intravascular coagulation (DIC) in these patients appears to be clear. We report the suppressive effect of interleukin-10 (IL-10) on endotoxin-induced TF activity and antigen levels, and on the expression of TF mRNA levels in human monocytes. These results emphasize the potential therapeutic value of this cytokine in septic shock, a condition still associated with a high mortality rate.

Humans↗

PubMed1993

Pentoxifylline inhibits the expression of tissue factor mRNA in endotoxin-activated human monocytes.

Tissue factor (TF) is a transmembrane glycoprotein which, in association with factor VII(a), is the main activator of coagulation. In illnesses such as Gram-negative endotoxemia, circulating monocytes synthesize and express substantial TF activity, resulting in extensive disseminated intravascular coagulation. We investigated the way in which TF is suppressed by pentoxifylline (PTX), and found that PTX down-regulates immunologic TF expression and specific mRNA production in response to LPS. Since TF mRNA stability is not altered, this effect appears to take place at the transcriptional level.

Endotoxins↗

PubMed1993

New assay for the rapid determination of plasma holotranscobalamin II levels: preliminary evaluation in cancer patients.

We describe a new and rapid assay for the measurement of plasma B12 bound to transcobalamin II (holotranscobalamin II) using the property of adsorption of the polypeptides of apotranscobalamin II and holotranscobalamin II to the hydrophobic surface of microfine glass particles. Acid-washed microfine glass was used to separate vitamin B12 bound to the glycoproteins transcobalamin I and transcobalamin III (haptocorrin or R binder) from that bound to transcobalamin II. Sephadex gel filtration separation of 57Co-labelled vitamin B12 binders confirmed that > 90% of holotranscobalamin II can be removed from plasma holohaptocorrin by adsorption to microfine glass particles. Since only holotranscobalamin II is capable of delivering vitamin B12 to metabolizing cells, plasma holotranscobalamin II content reflects the availability of B12 to cells. Use of this test in cancer patients undergoing either chemotherapy or radiation therapy revealed evidence of early negative B12 balance that in some instances was induced by the treatment itself.

Adsorption↗

PubMed1993

Measurement of red blood cell-vitamin B12: a study of the correlation between intracellular B12 content and concentrations of plasma holotranscobalamin II.

We have recently reported a new and rapid assay to measure plasma holotranscobalamin II (holo TC II) as a means of exploring vitamin B12 status. In order to further evaluate the significance of plasma holoTC II in determining tissue cobalamin, we have chosen the red blood cell-vitamin B12 (RBC-B12) assay as a measure of tissue vitamin B12 content and studied the relationship between RBC-B12 and plasma holoTC II levels. Plasma holoTC II and RBC-B12 concentrations were concomitantly assayed in 20 hematologically normal controls and cancer patients. In our groups of controls, the mean value of RBC-B12 was determined as 241 +/- 51 pg/ml of packed erythrocytes (PE) with a range varying from 180 to 355 pg/ml PE. Preliminary results obtained in 32 cancer patients revealed lower holoTC II and RBC-B12 levels than the control group and a required threshold value of 70 pg/ml of holoTC II in order to maintain a normal RBC-B12 greater than 180 pg/ml PE.

Erythrocytes↗