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Biomedical subjects

N Lee

Publications and source records attributed to N Lee.

At least 145 records · Page 8Linked to original sources
PubMed1996

Pre-clinical development of the anti-tumour agent CB 7646, bis N-(hydroxymethyl) trimethylmelamine, a stable analogue of trimelamol.

Formulation difficulties prevented the otherwise promising clinical development of the anti-tumour agent trimelamol (TM; tris-[hydroxymethyl]trimethylmelamine]). A synthetic analogue programme resulted in the identification of CB 7646 (bis N-[hydroxymethyl]trimethylmelamine) as a compound with improved stability and favourable formulation characteristics. The in vitro and in vivo activity of CB 7646 was shown to be very similar to that of TM. In addition, curative activities were shown in the PXN/65 human ovarian cancer xenograft and the MX-1 and T-61 human breast cancer xenograft models. The effectiveness of the N-(hydroxymethyl)melamines against platinum-refractory disease was noted in the phase I clinical trial of TM. In line with this finding, the present study confirmed the effective activity of both TM and CB 7646 against various forms of platinum resistance in in vitro models. Curative activity for TM and CB 7646 was seen in the HX110P human ovarian cancer xenograft with acquired carboplatin resistance. Animal studies indicated less neurotoxicity for CB 7646 than for TM. The pharmacokinetic profile of CB 7646 indicated a decreased plasma elimination, indicative of slower in vivo degradation than for TM. CB 7646, therefore, represents a promising candidate for clinical development, designed to supersede TM.

Animals↗
PubMed1996

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery.

We prospectively studied immune reconstitution in 102 children who underwent T-lymphocyte depleted bone marrow transplants using either closely matched unrelated donors or partially matched familial donors by assaying total lymphocyte counts (TLC), T-cell subsets, B cells, and natural killer cells. TLC, CD3+, and CD4+ T-cell counts remained depressed until 2 to 3 years posttransplant, whereas CD8+ T-cell counts normalized by 18 months, resulting in an inverted CD4:CD8 ratio until 12 months posttransplant. Although the percentage of NK cells was elevated early posttransplant, their absolute numbers remained normal. CD20+ B cells were depressed until 12 to 18 months posttransplant. Factors affecting immunophenotypic recovery were analyzed by nonparametric statistics. Younger patients tended to have higher TLC posttransplant. Higher marrow cell doses were not associated with hastened immunophenotypic recovery. Graft-versus-host disease (GVHD) and/or its treatment significantly delayed the immune reconstitution of CD3+, CD4+, and CD20+ cells. The presence of cytomegalovirus was associated with increased CD8+ counts and a decrease in the percentages of CD4+ and CD20+ cells.

Adolescent↗
PubMed1996

Thymocyte cell fate alteration by high levels of CD8alpha is independent of CD8-lck association.

CD8 expression on the surface of developing thymocytes is essential for the positive selection and maturation of CD8 single positive T cells. CD8 is physically associated with the cytoplasmic tyrosine kinase, p56lck and, in addition to increasing the avidity between the TCR and MHC/peptide complex, may transduce intracellular signals. Here we address the extent to which the requirement for CD8 in thymocyte selection depends on its capacity to signal vs its contribution to avidity. We have previously reported that elevated levels of CD8alpha can alter the fate of developing 2C TCR+ thymocytes from positive to negative selection in H-2b mice. We show here that the fate of 2C TCR thymocytes overexpressing a mutant form of CD8alpha that does not bind to p56lck is the same as that of thymocytes overexpressing the wild-type CD8alpha-chain. This finding demonstrates that, for a TCR-MHC system in which the level of CD8alpha is the deciding factor in cell fate, negative selection does not require increased CD8-dependent signaling through p56lck. We have also found that highly elevated levels of CD8alpha expression (10-fold) block thymocyte maturation in both CD8alpha single and CD8alpha/HY TCR double transgenic mice. Although these may be additional examples of CD8alpha overexpression altering cell fate from positive to negative selection, we present arguments in favor of the interpretation that high levels of CD8alpha actually may block positive selection.

Animals↗
PubMed1996

Immunohistochemical localization of ciliary neurotrophic factor receptor alpha expression in the rat nervous system.

Ciliary neurotrophic factor receptor alpha (CNTFR alpha) is essential for normal embryonic development and may be involved in postnatal and adult neuronal maintenance. In addition, a rapidly growing body of evidence suggests that CNTFR alpha serves as a site of action for future growth factor therapeutics capable of treating a wide variety of disorders resulting from neuronal loss. We raised two polyclonal, anti-CNTFR alpha antisera against synthetic peptides corresponding to independent regions of rat CNTFR alpha. Western blot and immunohistochemical analyses indicated that affinity-purified preparations of both antisera specifically recognize CNTFR alpha. In the adult brain, the highest levels of CNTFR alpha immunoreactivity were found in the perikarya, dendrites and, occasionally, the axons of several distinct classes of neurons including hippocampal formation neurons, some sensory neurons, and many neurons involved in motor control. CNTFR alpha immunoreactivity also was concentrated in the following: perikarya, dendrites, and axons of ventral horn motor neurons in adult spinal cord; perikarya and axons of adult dorsal root ganglion neurons; and axons in adult peripheral nerve. In embryonic tissue, the highest levels of CNTFR alpha immunoreactivity were observed in differentiating neurons and their processes. Therefore, the present data suggest that CNTFR alpha serves several diverse functions in adulthood and during development.

Amino Acid Sequence↗
PubMed1996

Deterministic model of DNA gel electrophoresis in strong electric fields.

We present a new model for the motion of a megabase-long DNA molecule undergoing gel electrophoresis. We assume that the dynamics of large segments of DNA is almost deterministic and can be described by a set of simple mechanical equations. This allows the numerical study of gel electrophoresis of ultra-high molecular weight DNA. A strong electric field forces DNA in a gel into a tree-like structure with branches-loops of different sizes. We determined the loop-size distribution function. This distribution has a power law form, confirming the hypothesis of the statistical self-similarity of a moving polymer. We find periodic configuration changes in the motion of a circular polymer, with the average period proportional to the molecular weight. During the period, a polymer goes through three distinct phases: a simple V-shape configuration, a growing tree, and a decaying tree. For a linear polymer this periodicity is much less pronounced because of additional perturbations to the dynamics caused by free ends. A circular polymer stays in a simple V-shaped configuration about 30% of the time, independent of molecular weight (10% for a linear polymer).

Computer Simulation↗
PubMed1996

"MECCA": a developmental, dose-intensive, non-cross-resistant platinum-based chemotherapy for advanced ovarian cancer.

Twenty-nine women, ages 30-58 years, with advanced ovarian carcinoma were treated with a developmental combination chemotherapy regimen consisting of mitomycin C, etoposide, cisplatin, and carboplatin (MECCA). This protocol utilized the concepts of dose intensity, front-end loading, non-cross-resistance, and synergy. The median overall survival was 37 months with a 27% 5-year survival; the median failure-free survival was 15 months with a 14% 5-year failure-free rate. The predominant toxicity was hematologic and there was one toxic death (cardiac failure). The overall survival results are superior to our previous experience.

Adult↗
PubMed1996

Lipaemia retinalis: a question of chylomicrons?

Lipaemia retinalis is a rarely described condition which occurs in certain types of both primary and secondary hyperlipidaemia. It presents with a striking fundal appearance. We report 7 cases of lipaemia retinalis and ocular manifestations in hyperlipidaemia which presented over a 12 year period to our hospitals. These illustrate the different presentations and stages of the disease, and other fundal abnormalities seen in hyperlipidaemia.

Adult↗
PubMed1996

High response rates with short infusional 2-chlorodeoxyadenosine in de novo and relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group.

Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non-Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell, follicular mixed cell, and lymphoplasmacytoid) were treated with 2-chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion) for an average of three cycles. Minor treatment delays, generally due to haematological toxicities, occurred in nine of 105 cycles. Major toxicities were lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred in seven patients. Overall response rate was 69% (five complete, 19 partial) reaching 88% for de novo patients (two complete, five partial). Elevated beta 2-microglobulin level was negatively predictive of response (P = 0.0014). Eight of 24 responders relapsed, with a median follow-up of 13 months. 2CdA administered as an intermittent infusion shows considerable single-agent activity in low-grade lymphomas achieving high response rates of prolonged duration. Consideration of schedules where 2CdA is alternatively administered with combination chemotherapy appears warranted.

Adult↗
PubMed1996

Determination of optimal liquid medium for enzyme expression by Helicobacter pylori.

AIMS: To determine the best medium for the growth and enzyme expression of Helicobacter pylori. METHODS: Twelve H pylori isolates from histologically confirmed infected patients were cultured on Brucella broth (BB), Brucella broth minus bisulphite (BLBB), and brain-heart infusion broth (BHIB), all supplemented with 5% (v/v) fetal calf serum. Growth rates and enzyme expressions of all H pylori isolates cultivated in these media were evaluated. RESULTS: Although both BLBB and BHIB supported good growth of H pylori under microaerophilic conditions, the total protein content of H pylori detected was much higher with BHIB cultivation. Measurement of the specific activities of urease, phospholipase C, and sphingomyelinase for 12 H pylori isolates cultivated in these media, showed that BHIB supported the highest expression of these enzymes. Although BLBB supported better growth of H pylori than BB, it did not increase enzyme expression. CONCLUSIONS: Cultivation of H pylori in BHIB is recommended for studies on the physiology, metabolism, and enzyme expression of the organism.

Animals↗
PubMed1996

Superinfection with hepatitis C virus in hemodialysis patients with hepatitis B surface antigenemia: its prevalence and clinical significance in Taiwan.

A survey of hepatitis B surface antigen (HBSAG) and antibodies against hepatitis C virus (anti-HCV) in 173 patients undergoing hemodialysis in Taiwan revealed that 15 (9%) patients were positive for both HBSAG and anti-HCV, 106 (61%) were positive for anti-HCV alone, and 14 (8%) were positive for HBSAG alone. Most HBSAg positivity was acquired before the onset of hemodialysis. Anti-HCV positivity, however, was mainly acquired via the hemodialysis procedure. Patients with dual markers were younger (43.7 +/- 3.3 years old, p = 0.0274), had the longest period on hemodialysis (6.6 +/- 1.3 years, p < 0.001), and more severe liver dysfunction. When compared with those who were negative for both markers, patients with both HBSAG and anti-HCV had an increased incidence of chronicity (5/15 vs. 2/38; p < 0.05), ultrasonographic cirrhosis (5/15 vs. 1/38; p < 0.05), and clinical decompensation (2/15 vs. 0/38; p < 0.05). Their risk for developing ultrasonographic cirrhosis and clinical decompensation was also greater than that of patients with anti-HCV alone (5/15 vs. 8/106 and 2/15 vs. 2/106; p < 0.05 for both). The presence of HBSAG alone, however, did not increase the incidence of liver dysfunction. The presence of anti-HCV alone was only associated with a greater elevation of serum alanine aminotransferase (44.2 +/- 5.5 vs. 19.1 +/- 2.5 U/l; p < 0.05) and an increased incidence of chronicity (30/106 vs. 2/38; p < 0.05). Our results indicate that a high prevalence of HCV superinfection impose a significant risk on a large population of HBSAG-positive hemodialysis patients in Taiwan. As the coexistence of anti-HCV and HBSAG is associated with more severe liver dysfunction, it is urgent to devise effective methods to prevent HCV circulation in a hemodialysis environment-especially in a hepatitis B virus endemic area such as Taiwan.

Adolescent↗
PubMed1996

Microbiologic assay for detection of antimicrobial agents in urine.

Antimicrobial therapy can be a confounding factor in the diagnosis of urinary tract infection and is not always reported to laboratories by physicians. We developed a microbiologic assay for screening urine specimens for antimicrobial agents. Bacillus stearothermophilus was used as the indicator bacteria. A total of 1,921 urine specimens from three hospitals in Taiwan were screened using this assay. Of the samples assayed, 1,293 were positive for antimicrobial agents. Agreement between information provided by physicians and laboratory findings was 68.5% (419/612). In the presence of antimicrobial agents in the urine samples, the isolation of yeasts and Pseudomonas aeruginosa increased dramatically, from 4.5 to 19.5% and 4.2 to 13.2%, respectively. Additionally, Escherichia coli was more resistant to gentamicin (75.3% vs 48.7%, p < 0.0001), norfloxacin (85.2% vs 64.6%, p = 0.0006) and co-trimoxazole (58.5% vs 35.5%, p = 0.0018). In view of the high rate of occurrence of antimicrobial agents in urine specimens and the lack of information provided by most physicians to laboratories, a screening method to detect the presence (or absence) of antimicrobials in urine specimens may be a useful tool particularly in areas such as Taiwan where antimicrobial agents are commonly abused.

Anti-Bacterial Agents↗