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T Le

Publications and source records attributed to T Le.

At least 37 records · Page 2Linked to original sources
PubMed2003

Early ovarian cancer: what is the staging impact of retroperitoneal node sampling?

BACKGROUND: Comprehensive surgical staging of apparent early-stage epithelial ovarian cancer includes peritoneal washings, biopsies, and retroperitoneal lymph node dissection. Unresolved is the relative frequency or importance of the lymph node dissection. OBJECTIVES: (1) To determine the site(s) of microscopic metastatic disease in women undergoing a comprehensive staging for apparent early-stage cancer of the ovary; (2) to identify those women with metastases in the retroperitoneal lymph nodes alone. METHODS: Between 1985 and 2000, we reviewed all records of women at cancer centres in Winnipeg, Ottawa, and Saskatoon who had undergone a "staging laparotomy" for an apparent early-stage IA epithelial cancer of the ovary. Histology, tumour grade, initial and final surgical stage, and the site(s) of metastatic disease were recorded for all cases. RESULTS: Forty-three of the 128 women (34%) had a final surgical stage of II or III. Sixteen women had positive pelvic biopsies, while 19 had microscopic upper abdominal disease. Eight women had positive retroperitoneal nodes, and in only 2 of these women, disease was found in the retroperitoneal nodes alone. In the 8 women with nodal disease, 5 had grade 3 tumours and 6 had serous histology tumours. CONCLUSION: Comprehensive staging is important to identify women with metastatic disease. Solitary nodal metastases are predominantly found in grade 3 and serous tumours.

Adenocarcinoma, Clear Cell↗
PubMed2003

Quality-of-life issues in patients with ovarian cancer and their caregivers: a review.

UNLABELLED: Significant progress has been made towards the treatment of ovarian cancer resulting in longer median survival despite a persistent low cure rate. Relatively few studies have examined the impact of the cancer and its treatment on the patients and their caregivers due to the difficulty in the definition and measurement of the Quality of Life (QOL) concept. A review of the literature revealed significant alterations in the quality of life of ovarian cancer patients during treatment and long term follow ups. For the caregivers, it is important for health care providers to realize that: 1) caregivers are being asked to assume an increasing number of complex care giving tasks at home, 2) there exists a high proportion of unmet caregiver needs, 3) the care giving experience includes both positive and negative elements and, 4) perception of caregivers' burden is positively linked to negative reactions to care giving. Supportive programs for patients and caregivers should be designed with these needs in mind. Future research should study the best way to incorporate results of quality of life assessments into routine treatment decision-making. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to outline the current data on QOL issues in patients with ovarian cancer, and to describe potential working definitions of QOL.

Caregivers↗
PubMed2003

Glucocorticoid receptors are downregulated in hepatic T lymphocytes in rats with experimental cholangitis.

BACKGROUND: and aims: Primary sclerosing cholangitis is a Th1 cytokine driven disease with a poor clinical responsiveness to glucocorticoid therapy. We have previously documented elevated circulating glucocorticoid levels in cholestatic rats and in addition have noted increased hepatic expression of the Th1 cytokine interferon gamma (IFN-gamma) in a rat model of cholangitis. Therefore, we examined the relationship between circulating glucocorticoid levels, hepatic IFN-gamma expression, and hepatic T cell glucocorticoid receptor (GR) expression in a rat model of cholangitis to provide insight into the possible mechanism underlying hepatic T cell glucocorticoid resistance in cholangitic diseases. METHODS: Cholangitis was induced in male Sprague-Dawley rats by oral administration of low dose alpha-naphthylisothiocyanate (ANIT). On day 14, ANIT fed and control rats were sacrificed, serum collected, and hepatic, splenic, and peripheral blood T lymphocytes isolated for GR expression, as determined by reverse transcription-polymerase chain reaction and western blotting. RESULTS: Circulating glucocorticoid levels were markedly elevated in ANIT fed rats. Hepatic T lymphocyte GR mRNA and protein levels were significantly reduced in ANIT treated rats compared with controls. In contrast, GR mRNA and protein expression in splenic and circulating T lymphocytes was similar in both groups. Furthermore, reduced hepatic T cell GR expression in ANIT fed rats was associated with reduced hepatic CD4(+) T cell sensitivity to dexamethasone inhibitory effects (that is, inhibition of interleukin 2 receptor expression). CONCLUSION: We conclude that hepatic T lymphocyte resistance to elevated endogenous glucocorticoid levels in rats with experimental cholangitis appears, in part, to be mediated by decreased GR expression.

1-Naphthylisothiocyanate↗
PubMed2002

Description of a novel HLA-DRB1 allele, DRB1*1207.

A new DRB1 allele has been identified during routine HLA-DRB1 generic typing with sequence specific oligonucleotides. The new allele was confirmed by PCR-restriction fragment length polymorphism analysis and subsequently sequenced. This showed the novel allele, named HLA-DRB1*1207, was similar in sequence to DRB1*12011, except for codon 69 of exon 2.

Alleles↗
PubMed2002

Six new HLA class I alleles detected by PCR-SSO genotyping.

This paper describes six new alleles; A*0240, A*2614, B*3924, B*4425, Cw*0807 and Cw*12023, which were discovered during routine genotyping with sequence specific oligonucleotides (SSO's). Five of the new alleles have changes in residues which belong to the antigen binding site of the HLA protein. These new variants may have altered antigen binding properties and may cause differential immunological responses that could affect transplantation outcome1.

Base Sequence↗
PubMed2002

Alternative end-joining in follicular lymphomas' t(14;18) translocation.

T(14;18) chromosomal translocation is assumed to result from illegitimate rearrangement between the BCL2 proto-oncogene and the IGH locus during the D(H) to J(H) joining phase of V(D)J recombination in early B cells. Analysis of the breakpoint junctions suggests that translocation derives from the fusion between normal V(D)J recombination intermediates at the IGH locus and non-V(D)J-mediated broken-ends at the BCL2 locus. So far, BCL2 broken-ends have only been observed fused to coding-ends, raising questions concerning the molecular constraints of the illegitimate joining process. Using a combination of genome walking and long-range PCR assays, we describe in this report that in 4.5% (2/44) of the t(14;18), one of the BCL2 broken-ends is fused to a signal-end. The formation of these J(H)RSS/BCL2 junctions provides direct evidence that BCL2 broken-ends are capable of joining to both products of V(D)J recombination, suggesting their presence in the RAG-mediated post-cleavage complex. In addition, junctions generated by this alternative end-joining do not involve deletion of the chromosome 14 intervening sequences generally lost in the standard translocation, providing a unique opportunity to investigate the rearrangement status of this region in the translocated IGH allele. In both cases, a DJ(H) rearrangement could be detected 5' of the J(H)-RSS/BCL2 junction. These findings, together with the previously reported bias towards the most external D(H) and J(H) segments in standard breakpoints, strongly suggest that t(14;18) preferentially occurs during an attempted secondary D(H) to J(H) rearrangement. This unusual and restricted window of differentiation opens intriguing questions concerning the etiology of the translocation.

Base Sequence↗
PubMed2001

Effect of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of P carinii pneumonia in patients with HIV-1: a prospective study.

BACKGROUND: Investigators have reported that patients infected with Pneumocystis carinii containing mutations in the DHPS (dihydropteroate synthase) gene have a worse outcome than those infected with P carinii containing wild-type DHPS. We investigated patients with HIV-1 infection and P carinii pneumonia to determine if DHPS mutations were associated with poor outcomes in these patients. METHODS: We compared presence of mutations at the DHPS locus with survival and response of patients to co-trimoxazole or other drugs. FINDINGS: For patients initially given co-trimoxazole, nine (14%) of 66 with DHPS mutant died, compared with nine (25%) of 36 with wild type (risk ratio50.55 [95% CI=0.24-1.25]; p=0.15). Ten (15%) of 66 patients with a DHPS mutant did not respond to treatment, compared with 13 (36%) of 36 patients with the wild type (0.42 [0.20-0.86]; p=0.02). For patients aged 40 years or older, four (14%) of 29 with the mutant and nine (56%) of 16 with the wild type died (0.25 [0.09-0.67]; p=0.005). INTERPRETATION: These results, by contrast with those of previous studies, suggest that patients with wild-type P carinii do not have a better outcome than patients with the mutant when given co-trimoxazole. Our results suggest that presence of a DHPS mutation should be only one of several criteria guiding the choice of initial drug treatment of P carinii pneumonia in patients with HIV-1 infection.

AIDS-Related Opportunistic Infections↗
PubMed2001

Cloning, genetic characterization, and chromosomal mapping of the mouse VDUP1 gene.

VDUP1 encodes a vitamin D3-inducible gene product that has been shown to be down-regulated in chemically-induced mammary tumors in rats. It has recently been reported to negatively regulate thioredoxin expression and function. We have cloned the mouse VDUP1 gene and characterized its genomic locus. The VDUP1 coding region spans eight exons within a total length of 2.3 kb located on mouse chromosome 3. Consensus sites for polyadenylation were identified 1.3 kb downstream of the gene, defining a long 3' untranslated region. The minimal functional VDUP1 promoter contains TATA and CCAAT boxes and transcription is initiated from two major start sites downstream. A direct repeat element located proximal to the TATA with homology to the USF binding site was identified as a potential regulator of VDUP1gene expression. Expression analysis determined that VDUP1 mRNA was markedly induced in myeloma cells in high density cell culture, but not in sub-confluent cells arrested by serum deprivation. All samples of a panel of mouse immortalized or transformed cell lines were shown to express abundant levels of VDUP1 mRNA.

Animals↗
PubMed2001

Increased midbrain 5-HT1A receptor number and responsiveness in cholestatic rats.

Midbrain somatodendritic 5-HT1A autoreceptors play a central inhibitory role in the regulation of serotonergic neurotransmission. Given that serotonergic neurotransmission appears to be altered in experimental cholestatic liver disease we examined alterations in midbrain 5-HT1A autoreceptor binding and physiological responses in rats with experimental cholestatic liver disease in comparison to non-cholestatic controls. Using a standard receptor binding assay cholestatic rats exhibited an increase in midbrain 5-HT1A receptor number but no change in receptor affinity compared to controls. Midbrain 5-HT1A receptor mRNA expression as determined by semiquantitative RT-PCR was similar in cholestatic and non-cholestatic animals. In addition, cholestatic rats exhibited enhanced 5-HT1A autoreceptor-mediated hypothermic and hyperphagic responses compared to non-cholestatic controls after the administration of the highly specific 5-HT1A receptor agonist LY293284. These findings indicate that experimental cholestatic liver injury is associated with enhanced 5-HT1A autoreceptor-mediated physiological responsiveness in the setting of increased midbrain 5-HT1A receptor number but not affinity.

Animals↗
PubMed2001

Templated nucleotide addition and immunoglobulin JH-gene utilization in t(11;14) junctions: implications for the mechanism of translocation and the origin of mantle cell lymphoma.

The t(11;14)(q13;q32) between the BCL-1 and immunoglobulin heavy chain gene (IgH) loci in mantle cell lymphoma (MCL) are believed to be mediated by the mechanism of V(D)J recombination similar to the t(14; 18) in follicular lymphoma (FL). We have recently shown that the t(14;18) event creates staggered double-strand breaks in the BCL-2 locus, and that the t(14;18) junctions contain templated nucleotide insertions (T-nucleotides; U. Jäger et al., Blood, 95: 3520-3529, 2000). Reasoning that the earlier (pregerminal center) B-cell origin of MCL might be reflected in a different molecular structure of the chromosomal breakpoints, we PCR-amplified diagnostic samples from 93 patients. Thirty-six samples (39%) were positive for the direct (BCL-1/J(H)) and 23 for both direct and reciprocal (D(H)/BCL-1) junctions. The breaks on chromosome 14 exhibited features of V(D)J-mediated recombination as shown by D(H) and J(H) coding end processing. However, duplications of BCL-1 sequences in 39% of the 23 patients indicate staggered double-strand breaks in the major translocation cluster region (MTC). This is incompatible with V(D)J recombination and indicates a different mechanism of cleavage. The use of J(H)6 in the junctions (39%) was similar to that in the immunoglobulin genes of normal B cells and B-CLL, but considerably less than in FL. Only 2 of 36 samples contained a BCL-1/DJ(H) rearrangement, which was indicative of a previous DJ(H) rearrangement. Most importantly, 19% of the BCL-1/IgH junctions with inserts of > or =5 nucleotides contained error-prone copies (T-nucleotides) of 8-12 nucleotides originating from the surrounding BCL-1 or IgH regions, a lower rate than in FL. No correlation was found between the addition of T-nucleotides and the rate of somatic mutation in the immunoglobulin genes. We conclude that the t(11;14) and t(14;18) use the same basic mechanism of translocation including V(D)J-mediated recombination, double-strand staggered breaks, and template-dependent, error-prone DNA-synthesis. However, the distinct differences in the utilization of J(H) regions suggest that the t(11;14) occurs predominantly during an attempted primary D(H)-J(H) rearrangement in early B cells, whereas the t(14;18) mostly occurs during secondary rearrangement. This is in agreement with the pregerminal center B-cell origin of MCL.

Base Sequence↗
PubMed2001

Recurrent metastatic fallopian tube carcinoma in pregnancy.

BACKGROUND: Fallopian tube cancer is the rarest of all gynecologic cancers. An extensive literature search on Medline reveals no previous case reports of fallopian tube carcinoma in association with a term pregnancy. CASE: A woman with surgical stage IIB fallopian tube carcinoma was treated with limited staging laparotomy, as per the patient's fertility wishes, followed by adjuvant cis-platinum and paclitaxel (Taxol). One year following chemotherapy, she conceived. She was noted to have an asymptomatic intraabdominal recurrence at 16 weeks. The patient completed 37 weeks of pregnancy without further therapy according to her wishes. She subsequently underwent a cesarean section with optimal tumor reduction surgery. Carboplatin and paclitaxel were reinstituted, achieving partial response. She is presently alive with stable disease status 6 months after completing her salvage chemotherapy. CONCLUSION: This is the first case report of recurrent fallopian tube cancer in pregnancy.

Abdominal Neoplasms↗
PubMed2001

Determination of grayanotoxins in biological samples by LC-MS/MS.

A rapid LC-MS/MS method was developed for the quantitative determination of grayanotoxins I, II, and III in rumen contents, feces, and urine. The grayanotoxins were extracted from solid samples with methanol. The methanol extract was diluted with water and cleaned up using a reversed phase solid phase extraction column. HPLC separation was performed by reversed phase HPLC using a gradient of water and methanol containing 1% acetic acid. Determination was by positive ion electrospray ionization and ion trap tandem mass spectrometry. Grayanotoxin I quantitation was based on fragmentation of the sodium adduct ion at m/z 435 to a product ion at m/z 375. Grayanotoxins II and III were quantitated on the basis of fragmentation of the ion at m/z 335 to the product ion at m/z 299. The method detection limits were 0.2 microg/g in rumen contents and feces and 0.05 microg/g in urine. Fortifications at the detection limits and 10 times the detection limits of bovine rumen contents, caprine feces, and ovine urine were recovered in the range 80-114%. The diagnostic utility of the method was tested by analyzing samples submitted to the veterinary toxicology laboratory.

Animals↗
PubMed2001

PCR-RFLP typing detects new HLA-DRB1 alleles: DRB1*13022, DRB1*1336 and DRB1*1435.

It is difficult to resolve all heterozygous combinations of the HLA-DRB1*03, *08, *11, *12, *13 and *14 allele group in a one-step generic HLA-DRB1 typing system. Therefore, it is common to employ a secondary technique utilizing group-specific primers to amplify this group of alleles separately from the other HLA-DRB1, -DRB3, -DRB4 and -DRB5 alleles. This paper describes a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for broad typing of the HLA-DRB1*03, *08, *11, *12, *13 and *14 alleles which, as well as being time-efficient and cost-effective, has so far allowed the detection of 10 new alleles. The new alleles were identified after following up unusual or novel PCR-RFLP patterns. Of the 10 novel alleles found so far with this method, seven have been described previously while three, DRB1*13022, DRB1*1336 and DRB1*1435, are presented here.

Alleles↗
PubMed2001

Adjuvant pelvic radiotherapy for uterine carcinosarcoma in a high risk population.

OBJECTIVES: The purpose of this study was to examine the clinical outcomes of patients with uterine carcinosarcoma and to review the role of adjuvant pelvic radiotherapy in the management of patients with high pathologic risk factors for recurrences. METHODS: A retrospective review was carried out at the Saskatoon Cancer Agency. All patients with a diagnosis of uterine carcinosarcoma from 1990-1995 were identified. Clinical and pathologic data were analysed in a computerized database. Kaplan-Meier survival estimates were computed. Log-rank test was used to compare survival curves and disease-free survival estimates. RESULTS: Thirty-two patients are reported. The median age at presentation was 71. Most patients presented with abnormal postmenopausal bleeding. Eighty-four percent of patients had disease confined to the uterus at the time of evaluation. Patients with high-grade (2, 3) adenocarcinoma, deep myometrial invasion, or gross pelvic metastatic disease were offered adjuvant pelvic irradiation. The overall 5-year survival for the whole group is 38%. There is no statistically significant difference in the progression-free or overall survival in the radiated group compared to the expectantly treated group. CONCLUSION: Uterine carcinosarcoma is a rare and aggressive form of uterine malignancy even in early stages. Adjuvant pelvic radiotherapy seems to improve the progression-free survival and overall survival in patients with poor histologic prognostic factors. The role of chemotherapy deserves further investigation as all recurrences were in the upper abdominal and distant locations outside of the radiation field. PRECIS: Uterine sarcoma has a poor prognosis even in early stage. Adjuvant pelvic radiotherapy seems to improve the outcomes of patients with adverse histologic risk factors.

Adult↗
PubMed2001

Effect of the interval between pregnancies on perinatal outcomes among white and black women.

OBJECTIVE: We evaluated interpregnancy interval in relation to adverse perinatal outcomes and whether the relationship differed by race. STUDY DESIGN: We analyzed the vital statistics data for multiparous white and black women in Michigan who delivered a singleton live birth during the period 1993 through 1998, using stratified and logistic regression techniques. RESULTS: Among women of both races, the risk for delivering low birth weight, premature, and small-for-gestational-age birth was lowest if the interpregnancy interval was 18 to 23 months. In comparison, among white women, the odds ratios for the 3 outcomes were 1.5, 1.3, and 1.3, respectively, if the interval was <6 months, and 1.9, 1.4, and 1.7, respectively, if the interval was > or =120 months, controlling for other factors. Similarly, among black women, the odds ratios were 1.5, 1.2, and 1.3, respectively, if the interval was <6 months, and 1.6, 1.3, and 1.4, respectively, if the interval was > or =120 months. CONCLUSION: An interpregnancy interval of 18 to 23 months is associated with the lowest risk for adverse perinatal outcomes among both white and black women.

Black or African American↗
PubMed2001

Folate status in women of childbearing age residing in Southern California after folic acid fortification.

OBJECTIVE: The purpose of this study was to investigate folate status in healthy, nonpregnant women (18 to 45 years) following folic acid (FA) fortification of the food supply. DESIGN: This was a cross-sectional study design in which a fasting blood sample was obtained from socio-economically advantaged (n=85) and disadvantaged (n=50) women residing in Southern California who had not consumed supplemental FA within the past 12 months. Serum folate (SF), red cell folate (RCF) and plasma homocysteine (tHcy) concentrations were measured and methylene tetrahydrofolate reductase (MTHFR) genotype (C677T) was determined. RESULTS: SF and RCF concentrations (mean+/-SD) for socio-economically advantaged (54+/-18, 1387+/-329 nmol/L, respectively) and disadvantaged women (41+/-18, 1172+/-342 nmol/L, respectively) greatly exceeded the levels deemed acceptable for SF (> or = 13.6 nmol/L) and RCF (> or = 362 nmol/L). Moreover, 95% of socio-economically advantaged women and 78% of disadvantaged women achieved RCF concentrations > or = 906 nmol/L, which are associated with very low risk of neural tube defects (NTD). Plasma tHcy concentrations for both socio-economically advantaged (5.2+/-1.6 micromol/L) and disadvantaged women (6.1+/-1.6 micromol/L) were within the lower limit of normal range and indicative of adequate folate status. For the combined groups (n=135), the frequency of the C/C, C/T and T/T genotype was 56.0, 37.3 and 6.7%, respectively. MTHFR genotype was not associated with SF, RCF or tHcy. CONCLUSIONS: These data suggest that women of childbearing age are achieving positive folate balance and RCF concentrations associated with reduced risk of NTD following FA fortification of the food supply.

Adolescent↗