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Biomedical subjects

T Mo

Publications and source records attributed to T Mo.

At least 19 recordsLinked to original sources
PubMed2006

Assay of HIV gp41 amino acid sequence to identify baseline variation and mutation development in patients with virologic failure on enfuvirtide.

In this study, we retrospectively assessed a gp41 genotypic assay in 404 enfuvirtide-naïve individuals (340 clade B, 64 non-B clade) to determine the prevalence of baseline polymorphisms and in 41 patients virologically failing enfuvirtide to determine correlates of resistance to this agent. Conserved and polymorphic regions of gp41 were identified in clade B isolates, with 127 of 328 codons (38.7%) being highly conserved (<1.0% variation) and 74 of 328 codons (22.6%) being partially conserved (1.0-5.0% variation). Polymorphisms were observed throughout gp41 in non-B clade virus sequences compared to the clade B reference strain, ranging from 53 natural substitutions in clade D to 76 in clade A. Insertions were common at positions 3, 105, 215 and 276. In the patients failing enfuvirtide, mutations were detected in the 10 amino acid region at positions 36-45 in all plasma virus sequences. Six additional mutations were selected outside of the common region which may be clinically significant at positions 33, 73, 75, 126, and 138. Two or three mutations at positions 36-45 were observed in the majority of plasma virus sequences from patients with virologic failure following the use of enfuvirtide. Further study is required to determine the clinical relevance of the clade related polymorphisms and the new mutations identified in the patients with virologic failure.

Adult↗
PubMed2001

HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort.

OBJECTIVE: To assess the effect of baseline HIV reverse transcriptase (RT) and protease sequence variation on virologic outcomes in a large cohort of antiretroviral-naive patients in British Columbia, Canada. METHODS: Population sequencing of RT and protease was performed on baseline viral RNA of all antiretroviral-naive patients first seeking treatment in British Columbia between June 1997 and August 1998 (n = 479). Relative risks of virological failure associated with genotypic differences from a 'standard' HIV strain (HXB2) were assessed for up to 18 months. RESULTS: The prevalence of key baseline mutations known to confer resistance to RT and protease inhibitors (PI) was 3.4 and 3.8%, respectively. No statistically significant impact on virologic outcomes could be established for these patients. However, the data suggest that some individuals (harboring a M184V mutation in RT or a V82I in protease) may have benefited from pre-therapy resistance tests. 'Secondary' mutations in the protease associated with resistance (e.g. codons 10, 36 or 63) were common, but the presence of these secondary mutations, either alone or in combination, did not appear to result in early loss of therapeutic virological suppression. Preliminary analyses suggest that an amino acid change at codon 35 in the protease may be associated with early treatment failure. CONCLUSIONS: The results suggest that routine genotyping of naive patients about to start antiretroviral therapy would be of benefit to a relatively small proportion of the population. Secondary mutations associated with resistance to PI alone were not found to affect virologic outcomes significantly.

Anti-HIV Agents↗
PubMed2000

Human immunodeficiency virus-infected persons with mutations conferring resistance to zidovudine show reduced virologic responses to hydroxyurea and stavudine-lamivudine.

The baseline predictors of poor virologic response (<0.5 log decrease in plasma virus load) were examined in two 1996 pilot trials of combination nucleoside-analogue therapy. One trial examined the addition of hydroxyurea to didanosine therapy; the other examined stavudine-lamivudine in combination. In both, predictors of virologic response included the presence of mutations associated with zidovudine resistance. For hydroxyurea, the odds ratio (OR) of failure to achieve a short-term (4 weeks) virologic response in a bivariate logistic regression model was 30.8 (95% confidence interval [CI], 1.75-543; P=.02) for use of lower dose hydroxyurea (500 mg/day) and 14.7 (95% CI, 1.1-200; P=.04) for the presence of a zidovudine-related mutation. For the stavudine-lamivudine study, the OR of failure to achieve a virologic response at 4 weeks in a multivariate logistic regression model was 23 (95% CI, 2.7-199; P=.004) for the presence of a mutation at codon 215.

Anti-HIV Agents↗
PubMed1999

Prevalence of primary HIV drug resistance among seroconverters during an explosive outbreak of HIV infection among injecting drug users.

OBJECTIVES: This study examined the frequency of transmission of drug resistant HIV in the population of injecting drug users (IDU) in Vancouver, Canada during a period of particularly high virus transmission. DESIGN: All subjects enrolled in the Vancouver Injection Drug Users Study who seroconverted from HIV negative to positive status (n = 61) between December 1996 and February 1998 were eligible for analysis. The first seropositive sample from 57 individuals with plasma samples available was analyzed for resistance to antiretroviral agents by population based sequencing of the HIV protease and reverse transcriptase genes. METHODS: Plasma viral RNA was extracted and the viral reverse transcriptase and protease regions were amplified by nested reverse transcription-PCR. The presence of mutations associated with antiretroviral drug resistance was assessed by automated sequence analysis. RESULTS: Protease and reverse transcriptase sequences were successfully obtained from the 57 recent seroconverters. No cases of transmission of variants associated with significant resistance to protease inhibitors or nucleoside and non-nucleosides reverse transcriptase inhibitors were detected. CONCLUSION: The frequency of transmission of drug resistant HIV amongst these recently infected IDU is extremely low, with no protease or reverse transcriptase inhibitor resistant strains detected soon after seroconversion. The data provide no rationale for withholding treatment from this already marginalized population.

Anti-HIV Agents↗
PubMed1999

[Left ventricular function evaluation after mitral valve replacement with preservation the subvalvular apparatus].

The objective of this study was to evaluate the left ventricular function after mitral valve replacement (MVR) with preservation of all chordae. Fourteen patients with a diagnosis of mitral regurgitation were studied. These patients, 4 males and 10 females, age from 24 to 59 years, who underwent mitral valve replacement, in which all chordae tendineae were preserved. The mean follow-up interval was 6 months. Preoperation and postoperation multigated equilibrium radionuclide angiography was performed by Elscint Helix Apex SPECT. Each patient was injected with 740MBq 99mTc-HSA, rest ejection fraction (global EF) of LV (%), regional ejection fraction (EF) of LV (%), PER/S and PFR/S were measured. Regional EF was calculated by the method of dividing the left ventricle into five segments by radial axis. The results showed that the postoperative EF of the whole left ventricle of the chordae-preserved patients was significantly greater than their preoperative EF (40.0% +/- 17.8%, to 51.6% +/- 18.2%, P < 0.02), and also the regional EF at the lateral wall of the chordae-preserved MVR was significantly greater than the preoperative regional EF (an increase from 51.0% +/- 18.1% to 69.7% +/- 21.2%, P < 0.01). MVR with preservation of all chordae, the patient's left ventricular function remarkably improved.

Adult↗
PubMed1995

Human immunodeficiency virus type 1 cellular RNA load and splicing patterns predict disease progression in a longitudinally studied cohort.

We report the results of a longitudinal study of RNA splicing patterns in 31 early-stage human immunodeficiency virus disease patients with an average follow-up time of 3 years. Eighteen patients showed no evidence for disease progression, whereas 13 patients either showed a > or = 50% reduction in baseline CD4 count or developed opportunistic infections. Levels of unspliced, tat, rev, and nef mRNAs in peripheral blood mononuclear cells were measured by a reverse transcriptase-quantitative, competitive PCR assay. Viral RNA was detected in all patients at all time points. All 13 rapid progressors had viral RNA loads that were > or = 1 log unit greater than those of the slow progressors. In addition, seven of the rapid progressors showed a reduction of more than threefold in the ratio of spliced to unspliced RNA over the 3 years of follow-up. Conversely, two slow progressors with intermediate levels of viral RNA showed no splicing shift. These results confirm earlier observations that viral RNA is uniformly expressed in early-stage patients. We further show that cellular RNA viral load is predictive of disease progression. Importantly, the shift from a predominately spliced or regulatory viral mRNA pattern to a predominately unspliced pattern both is associated with disease progression and adds predictive utility to measurement of either RNA class alone.

AIDS Vaccines↗
PubMed1995

[Effect of 153Sm-EDTMP on hematopoiesis and vital organs of 93 patients with bone tumor].

In the present study data on blood cell count, serum biochemistry, electrolyte, enzyme and vital organs of 93 patients with bone tumor or metastasis were investigated before and after treatment with 153Sm-EDTMP. The results showed that, 7 days and 30 days after the administration of 153Sm-EDTMP (< 29.6 MBq) (0.8 mCi/kg), the levels of hemoglobin, WBC lymphocyte count, and the liver and kidney function of all patients were not significantly different from the baseline data before treatment (P > 0.05). Although at 7 days, there was a declination of the granulocyte count, it returned to normal at 30 days (P > 0.05). The platelet count was significantly decreased (0.05 > P > 0.01). at 30 days after the administration of 153Sm-EDTMP. Thirteen patients received 74-185 MBq (2-5mCi/kg) and their myelo biopsies at 3 and 18 months showed no sign of acute or chronic toxicosis.

Adult↗
PubMed1995

[153Sm-EDTMP for moderate and severe bone cancer pain].

One hundred and thirty-six patients with bone cancer pain were treated with 153Sm-EDTMP (ethylenediamine-tetramethylene phosphonic acid). Pain free was noted in 49 cases (36%, 49/136) and pain relief in 77 cases (56.6%, 77/136), the total relief rate being 92.6% (126/136). The data from 76 patients with moderate and severe pain showed there were no significant relationships between the patients' age, the dose of 153Sm-EDTMP and the analgesic effects (P > 0.05). The pain relief observed in the patients with chest pain (ribs metastases) was earlier than that in other groups (P < 0.05). We didn't find any clinical side-effects, so 153Sm-EDTMP is safe for use.

Adult↗
PubMed1994

Accurate and differential quantitation of HIV-1 tat, rev and nef mRNAs by competitive PCR.

An accurate method is described for measuring the relative abundance of HIV-1 regulatory mRNAs directly in clinical specimens. Specimen RNA is reverse transcribed and coamplified with a common competitor containing tat, rev and nef internal standards using fluorescent primers and a competitive polymerase chain reaction. After amplification, individual products are separated and analyzed on a fluorescent DNA sequencer. Using this approach, it was possible to measure reproducibly two-fold differences in the relative abundance of mRNAs with coding potential for tat, rev and nef from as little as 0.2 ng of total RNA extracted from peripheral blood mononuclear cells of HIV-1 infected persons. The ratio method eliminates the need to account for variability in RNA recovery during sample processing and provides a powerful tool for measuring the differential expression of HIV-1 regulatory genes in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Evaluation of hepatitis C virus kits.

Hepatitis C virus (HCV) antibodies were detected in 85.9% of the samples by commercial enzyme immunoassay (EIA) kits. Most EIA-positive samples were reactive (80%) by the RIBA HCV test (Ortho Diagnostics). Samples with optical density values greater than or equal to 2.0 were mostly reactive (87%) by RIBA HCV test, in contrast to those with values less than or equal to 1.0 (6.6%). Samples which were indeterminate by the RIBA HCV test were positive (88.4%) by HCV neutralization EIA (Abbott Laboratories), along with 29.4% of samples which were nonreactive by the RIBA HCV test.

Evaluation Studies as Topic↗
PubMed1987

Effect of nonspecific interactions of the hepatitis B surface antigen with the solid phase on its detection by two-site immunoradiometric assay.

Two-site immunoradiometric assay (Austria II-125, procedure B, Abbott) was used to detect hepatitis B surface antigen (HBsAg) in chronic carrier sera from clinically healthy subjects or from kidney transplant or hemodialysis patients. The titration curves of some high-titered sera showed a prozone-like effect; this corresponded in two such sera LB and MA, to congruent to 80% inhibition of HBsAg detection in undiluted serum relative to a 1:800 dilution. The nature of the inhibition in the above two sera was investigated. We found that the inhibition depended on the time of first incubation but not on the affinity of capture antibodies. Nonspecific adsorption of HBsAg to the solid phase during the first incubation with inhibitory sera and elution of the thus adsorbed antigen during the second incubation, with the resulting neutralization of 125I-labeled anti-HBs, appeared to cause the inhibition of detection observed. The inhibition was prevented by addition of the detergent Triton X-100 to serum or by elution of adsorbed antigen prior to the second incubation, thus indicating that further improvements of the HBsAg immunoradiometric assay may be possible.

Adsorption↗