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Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 181 records · Page 10Linked to original sources
PubMed2002

Major colorectal cancer resection should not be denied to the elderly.

AIMS: Adjuvant therapy after surgery for colorectal cancer is often denied to the elderly for various reasons. This study was to determine morbidity and mortality risk after surgery in the elderly and whether this is affected by adjuvant therapy. METHODS: Data were collected prospectively and entered on a database for all patients undergoing resection of colorectal cancer between January 1994 and July 2000. A total of 304 patients were included, 65 aged 80 years and over. RESULTS: There were 84 deaths, 21 (30%) in the over 80s, and 63 (26%) in the under 80s (P=0.51). The 'in-hospital' mortality was 10.1% in the over 80s and 3.8% in the under 80s (P=0.056). In the over 80s the colon was more affected than the rectum (P=0.002). The over 80s were less likely to be offered adjuvant therapy, 7.2% vs 42.1% (P<0.001). The 5 year survival (all-cause mortality) in the over 80s was 58.5% and 47.6% in the under 80s (P=0.25). Cox's regression analysis of all patients identified the following factors to be independently related to overall survival: age>80 years, post-operative leak, increasing Dukes stage and distant recurrence of disease. CONCLUSION: This study has demonstrated that surgery should not be denied to elderly patients with colorectal cancer as despite a higher post-operative morbidity and mortality rate and with the absence of adjuvant therapy, favourable long-term outcome can be achieved by resectional surgery alone.

Adult↗
PubMed2002

Development of a closed-system process for clinical-scale generation of DCs: evaluation of two monocyte-enrichment methods and two culture containers.

BACKGROUND: Clinical immunotherapy trials using DCs depend on large-scale methods for DC generation that fulfil current good manufacturing practice requirements. Our goal was to develop data on two variables, monocyte-enrichment method and culture container, which could be used to design a closed-system process for ex vivo generation of immature DCs. METHODS: Mononuclear cells were collected by leukapheresis and enriched for monocytes by either counterflow centrifugal elutriation, or immunomagnetic selection using Isolex, an automated closed-system device. Monocytes were cultured for 7 days in serum-free medium with GM-CSF and IL-4, using either plastic flasks or gas-permeable Stericell bags. Monocytes and cultured DCs were evaluated for yield, flow cytometric phenotype, and in vitro function in MLR, and autologous recall responses to tetanus toxoid and influenza virus. RESULTS: Enriched monocyte products from elutriation and immunomagnetic selection were equivalent in yield and purity, and were capable of generating immature DCs in either flasks or bags. DCs from all four culture conditions were equivalent in yield, phenotype, and in vitro function. Mean DC yield was 67-80% per seeding monocyte, and 11-13% per starting mononuclear cell (MNC). A leukapheresis product containing 5 x 10(9) MNCs processed by this method could therefore yield approximately 5 x 10(8) immature DCs. DISCUSSION: In this manufacturing process, the Isolex system was equivalent to elutriation, and Stericell bags were equivalent to flasks. Together, the Isolex system and Stericell bags can be incorporated into a closed-system process to generate immature DCs.

Adoptive Transfer↗
PubMed2002

Phenotypic effects of somatic cell cloning in the mouse.

Although a variety of phenotypes and epigenetic alterations have been reported in animals cloned from somatic cells, the exact nature and consequences of cloning remain unclear. We cloned mice using fresh or short-term cultures of donor cells (cumulus cells, immature Sertoli cells, and fetal or adult fibroblast cells) with defined genetic backgrounds, and then compared the phenotypic and epigenetic characteristics of the cloned mice with those of fertilization-derived control mice. Irrespective of the nucleus-donor cell type, about 50% of the reconstructed embryos developed to the morula/blastocyst stage, but about 90% of these clones showed arrested development between days 5 and 8, shortly after implantation. Most of the clones were alive at term, readily recovered respiration, and did not show any malformations or overgrowths. However, their placentas were two- to threefold larger than those of the controls, due to hyperplasia of the basal (or spongiotrophoblast) layer. Although there was significant suppression of a subset of both imprinted and non-imprinted placental genes, fetal gene suppression was minimal. The seven imprinted genes that we examined were all expressed correctly from the parental alleles. These findings were consistent for every cell type from the midgestation through term stages. Therefore, cloning by nuclear transfer does not perturb the parent-specific imprinting memory that is established during gametogenesis, and the phenotypic and epigenetic effects of cloning are restricted to placental development at the midgestation and term stages. Twelve male mice that were born in a normal manner following nuclear transfer with immature Sertoli cells (B6D2F1 genetic background) were subjected to long-term observation. They died earlier than the genotype-matched controls (50% survival point: 550 days vs. 1028 days, respectively), most probably due to severe pneumonia, which indicates that unexpected phenotypes can appear as a result of the long-term effects of somatic cell cloning.

Animals↗
PubMed2002

Prevalence and risk factors associated with dry eye symptoms: a population based study in Indonesia.

AIM: To determine the prevalence and identify associated risk factors for dry eye syndrome in a population in Sumatra, Indonesia. METHODS: A one stage cluster sampling procedure was conducted to randomly select 100 households in each of the five rural villages and one provincial town of the Riau province, Indonesia, from April to June 2001. Interviewers collected demographic, lifestyle, and medical data from 1058 participants aged 21 years or over. Symptoms of dry eye were assessed using a six item validated questionnaire. Presence of one or more of the six dry eye symptoms often or all the time was analysed. Presence of pterygium was documented. RESULTS: Prevalence of one or more of the six dry eye symptoms often or all the time adjusted for age was 27.5% (95% confidence interval (CI) 24.8 to 30.2). After adjusting for all significant variables, independent risk factors for dry eye were pterygium (p<0.001, multivariate odds ratio (OR) 1.8; 95% CI 1.4 to 2.5) and a history of current cigarette smoking (p=0.05, multivariate OR 1.5; 95% CI 1.0 to 2.2). CONCLUSIONS: This population based study provides prevalence rates of dry eye symptoms in a tropical developing nation. From our findings, pterygium is a possible independent risk factor for dry eye symptoms.

Adult↗
PubMed2002

Effluents from a pulp and paper mill: a skin and health survey of children living in upstream and downstream villages.

OBJECTIVES: A health survey of three villages (upstream village Rantau Baru and two downstream villages, Sering and Pelalawan) in the vicinity of a pulp and paper mill along the Kampar river in the province of Riau, Indonesia was conducted to find whether exposure to the effluents from the mill was related to skin conditions and ill health. METHODS: A cross sectional survey was carried out of children living in the three villages. RESULTS: Common skin conditions such as dermatitis, fungal infections, insect bites, and miliaria were found. No significantly increased risk of dermatitis or any illness in general was found with increasing levels of exposure to river water for downstream villages when compared with the upstream village. However, there was an increased risk of diarrhoea in Sering especially with drinking water directly from the river (prevalence rate ratio (PRR) 4.9, 95% confidence interval (95% CI) 0.4 to 63.9). An increased risk was also found within the upstream village Rantau Baru (PRR 2.3, 95% CI 0.9 to 5.8) and downstream village Sering (PRR 1.4, 95% CI 0.4 to 5.2) when children who drank water directly from the river were compared with those who never did. Analysis of the river water also showed physical and chemical variables within the acceptable range except for faecal coliforms (6 MPN/100 ml) found in the sample taken from Sering. CONCLUSIONS: The effluent from the mill is unlikely to be causing skin conditions and ill health. Diarrhoea may be due to faecal coliform contamination of the water because all raw sewerage is deposited in the river. Community health outreach programmes are being implemented based on these findings.

Child↗
PubMed2002

Implementation of the British Thoracic Society recommendations for organising the care of patients with lung cancer: the surgeon's perspective.

BACKGROUND: The British Thoracic Society (BTS) recognises that it is of paramount importance to ensure that all patients with a working diagnosis of lung cancer have access to first class care [The Lung Cancer Working Party of the British Thoracic Society Standards of Care Committee. BTS recommendations to respiratory physicians for organising the care of patients with lung cancer. Thorax 1998; 53 (Suppl 1): S1-81. METHODS: A retrospective audit of the time involved in the management of patients with lung cancer referred for consideration of surgery at the Royal Brompton Hospital was carried out. Our performance was compared with the BTS recommendations. RESULTS: The notes from 194 patients were analysed, accounting for 93.7% of patients referred with lung cancer in a 1-year period. A total of 90 patients fulfilled the criteria for analysis as they had potentially resectable disease at referral; 59 (65.5%) underwent thoracotomy, and 31 (34.5%) were considered inoperable. The median interval between the onset of symptoms and their first chest radiograph was 39 days, and between the onset of symptoms and referral to a surgeon by a chest physician was 112 days. The median interval between referral by a respiratory physician and surgical out-patient attendance was 14 days, and between referral by a respiratory physician and the surgical procedure was 32.5 days. The median length of time from surgical out-patient attendance to the surgical procedure was 17 days. There was no association between the interval between the onset of symptoms and the surgical procedure with advanced tumour stage at surgery. CONCLUSIONS: There are a number of sources of delay in the referral process for a patient with potentially resectable lung cancer. Most patients referred to our unit were treated within the time scale recommended by the BTS. Our survey has shown that there are cumulative delays in the overall investigation and management of lung cancer patients, which are not covered by the BTS guidelines, and which result in unacceptable delays for most patients.

Adult↗
PubMed2002

First identification of a ranavirus from green pythons (Chondropython viridis).

Ten juvenile green pythons (Chondropython viridis) died or were euthanized shortly after having been illegally imported into Australia from Indonesia in 1998. Histologic examination of two of the three snakes that died revealed moderately severe chronic ulceration of the nasal mucosa and focal or periacinar degeneration and necrosis of the liver. In addition there was severe necrotizing inflammation of the pharyngeal submucosa accompanied by numerous macrophages, heterophils, and edema. An iridovirus was isolated in culture from several tissues and characterized by immunohistochemistry, electron microscopy, enzyme-linked immunosorbent Assay, polyacrylamide gel electrophoresis, polymerase chain reaction and sequence analysis, restriction endonuclease digestion, and DNA hybridization. This is the first report of a systemic ranavirus infection in any species of snake and is a new member of the genus, Ranavirus.

Amino Acid Sequence↗
PubMed2002

The nomographic design approach to recycled water reatment by the nitritation process.

The side-stream generated recycled water in the wastewater treatment plants is characterized as high in both nitrogen concentration and fluctuation of load. Thus, the design approach for recycle water management became an important part of the biological nutrient removal system design. The application of nitrogen removal from recycled water using the nitritation process has recently been increased due to economical reasons associated with an effective carbon allocation as well as the minimization of aeration cost. The concept of nitritation reactor design related to an inhibition of nitrite oxidizer has not been fully practiced in reality because of the limited field experiences. In this paper, a new approach has been proposed to determine reactor size and oxygen requirement in nitritation process design. The SRT-based design approach has been examined based on a series of laboratory experiments.

Bioreactors↗
PubMed2002

Formulation development of epidermal growth factor.

The information in this paper is presented to summarise various investigations in recent years to develop epidermal growth factor (EGF) delivery systems. EGF is a promising and well-characterised polypeptide that can be used in the treatment of various types of wounds and ulcers. Many approaches have been employed to deliver EGF as a stimulant for cellular activities involved in the processes of wound healing and tissue repair. Recently, emphasis is placed on the development of sustained or controlled delivery technology to optimise EGF delivery.

Animals↗
PubMed2001

Effective inhibition of herpes simplex virus 1 gene expression and growth by engineered RNase P ribozyme.

Using an in vitro selection procedure, we have previously isolated ribonuclease P (RNase P) ribozyme variants that efficiently cleave an mRNA sequence in vitro. In this study, an M1GS RNA variant was used to target the mRNA encoding human herpes simplex virus 1 (HSV-1) major transcription activator ICP4. The variant is about 15 times more efficient in cleaving the ICP4 mRNA sequence in vitro than the ribozyme derived from the wild type RNase P ribozyme. Moreover, the variant is also more effective in inhibiting viral ICP4 expression and growth in HSV-1-infected cells than the wild type ribozyme. A reduction of approximately 90% in the expression level of ICP4 and a reduction of 4000-fold in viral growth were observed in cells that expressed the variant. In contrast, a reduction of <10% in the ICP4 expression and viral growth was observed in cells that either did not express the ribozyme or produced a catalytically inactive ribozyme mutant. These results provide direct evidence that RNase P ribozyme variants can be highly effective in inhibiting HSV-1 gene expression and growth and furthermore, demonstrate the feasibility of developing highly effective RNase P ribozyme variants for anti-HSV applications by using in vitro selection procedures.

Animals↗
PubMed2001

Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes.

We have demonstrated previously the oncolytic effects of a systemically delivered, replicating vaccinia virus. To enhance the tumor specificity of this vector, we have developed a combined thymidine kinase-deleted (TK-) and vaccinia growth factor-deleted (VGF-) vaccinia virus and investigated its properties in vitro and in vivo. The gene for enhanced green fluorescent protein (EGFP) was inserted into the TK locus of a VGF- vaccinia virus by homologous recombination creating a double-deleted mutant vaccinia virus (vvDD-GFP). Infection of resting and dividing NIH3T3 cells with vvDD-GFP yielded reduced viral recovery compared with wild-type (WT), TK-, or VGF- viruses from resting cultures but equivalent virus recovery from dividing cultures. Eight days after nude mice were injected i.p. with 10(7) plaque-forming units (pfu) of WT, TK-, VGF-, or vvDD-GFP vaccinia virus, tissues and tumor were harvested for viral titer determination. No virus was recovered from the brains of mice injected with vvDD-GFP compared with the other viruses, which ranged from 130 to 28,000 pfu/mg protein; however, equivalent amounts were recovered from tumor. There was no toxicity from vvDD-GFP because nude mice receiving 10(8) pfu of IP vvDD-GFP lived >100 days, whereas mice receiving WT, VGF-, or TK- virus had median survivals of only 6, 17, and 29 days, respectively. Similar results were seen when 10(9) pfu of vvDD-GFP were given. Nude mice bearing s.c. murine colon adenocarcinoma (MC38) had significant tumor regression after treatment with 10(9) pfu of systemic (i.p.) vvDD-GFP compared with control (mean tumor size, 180.71 +/- 35.26 mm(3) versus 2796.79 +/- 573.20 mm(3) 12 days after injection of virus). Our data demonstrate that a TK- and VGF- mutant vaccinia virus is significantly attenuated in resting cells in vitro and demonstrates tumor-specific replication in vivo. It is a promising vector for use in tumor-directed gene therapy, given its enhanced safety profile, tumor selectivity, and the oncolytic effects after systemic delivery.

3T3 Cells↗
PubMed2001

Guided medication dosing for inpatients with renal insufficiency.

CONTEXT: Usual drug-prescribing practices may not consider the effects of renal insufficiency on the disposition of certain drugs. Decision aids may help optimize prescribing behavior and reduce medical error. OBJECTIVE: To determine if a system application for adjusting drug dose and frequency in patients with renal insufficiency, when merged with a computerized order entry system, improves drug prescribing and patient outcomes. DESIGN, SETTING, AND PATIENTS: Four consecutive 2-month intervals consisting of control (usual computerized order entry) alternating with intervention (computerized order entry plus decision support system), conducted in September 1997-April 1998 with outcomes assessed among a consecutive sample of 17 828 adults admitted to an urban tertiary care teaching hospital. INTERVENTION: Real-time computerized decision support system for prescribing drugs in patients with renal insufficiency. During intervention periods, the adjusted dose list, default dose amount, and default frequency were displayed to the order-entry user and a notation was provided that adjustments had been made based on renal insufficiency. During control periods, these recommended adjustments were not revealed to the order-entry user, and the unadjusted parameters were displayed. MAIN OUTCOME MEASURES: Rates of appropriate prescription by dose and frequency, length of stay, hospital and pharmacy costs, and changes in renal function, compared among patients with renal insufficiency who were hospitalized during the intervention vs control periods. RESULTS: A total of 7490 patients were found to have some degree of renal insufficiency. In this group, 97 151 orders were written on renally cleared or nephrotoxic medications, of which 14 440 (15%) had at least 1 dosing parameter modified by the computer based on renal function. The fraction of prescriptions deemed appropriate during the intervention vs control periods by dose was 67% vs 54% (P<.001) and by frequency was 59% vs 35% (P<.001). Mean (SD) length of stay was 4.3 (4.5) days vs 4.5 (4.8) days in the intervention vs control periods, respectively (P =.009). There were no significant differences in estimated hospital and pharmacy costs or in the proportion of patients who experienced a decline in renal function during hospitalization. CONCLUSIONS: Guided medication dosing for inpatients with renal insufficiency appears to result in improved dose and frequency choices. This intervention demonstrates a way in which computer-based decision support systems can improve care.

Decision Support Systems, Clinical↗
PubMed2001

Search for the familon via B(+/-) --> pi+/-X(0), B(+/-) --> K(+/-)X(0), and B(0) --> K(0)(S)X(0) decays.

We have searched for the two-body decay of the B meson to a light pseudoscalar meson h = pi(+/-),K+/-,K(0)(S) and a massless neutral feebly interacting particle X(0) such as the familon, the Nambu-Goldstone boson associated with a spontaneously broken global family symmetry. We find no significant signal by analyzing a data sample containing 9.7x10(6) BBbar mesons collected with the CLEO detector at the Cornell Electron Storage Ring, and set 90% C.L. upper limits italicB(B(+/-) --> h(+/-)X(0)) = 4.9x10(-5) and italicB(B(0) --> K(0)(S)X(0)) = 5.3x10(-5). These limits correspond to a lower bound of approximately 10(8) GeV on the family symmetry breaking scale with vector coupling involving the third generation of quarks.

Journal Article↗
PubMed2001

DNA recombination and RNA cleavage activities of the Flp protein: roles of two histidine residues in the orientation and activation of the nucleophile for strand cleavage.

Using a combination of DNA and hybrid DNA-RNA substrates, we have analyzed the mechanism of phosphoryl transfer by the Flp site-specific recombinase in three different reactions: DNA strand breakage and joining, and two types of RNA cleavage activities. These reactions were then used to characterize Flp variants altered at His309 and His345, amino acid residues that are in close proximity to two key catalytic residues (Arg308 and Tyr343). These histidine residues are important for strand cutting by Tyr343, the active-site nucleophile of Flp, but neither residue contributes to the type II RNA cleavage activity or to the strand-joining reaction in a pre-cleaved substrate. Strand cleavage reactions using small, diffusible nucleophiles indicate that this histidine pair contributes to the correct positioning and activation of Tyr343 within the shared active site of Flp. The implications of these results are evaluated against the recently solved crystal structure of Flp in association with a Holliday junction.

Amino Acid Substitution↗
PubMed2001

Conformationally constrained analogues of diacylglycerol. 18. The incorporation of a hydroxamate moiety into diacylglycerol-lactones reduces lipophilicity and helps discriminate between sn-1 and sn-2 binding modes to protein kinase C (PK-C). Implications for isozyme specificity.

An approach to reduce the log P in a series of diacylglycerol (DAG)-lactones known for their high binding affinity for protein kinase C (PK-C) is presented. Branched alkyl groups with reduced lipophilicity were selected and combined with the replacement of the ester or lactone oxygens by NH or NOH groups. Compound 6a with an isosteric N-hydroxyl amide arm represents the most potent and least lipophilic DAG analogue known to date.

4-Butyrolactone↗
PubMed2001

A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase).

Design, synthesis and structure-activity relationship of a class of aryl pyrroles as farnesyltransferase inhibitors are described. In vitro and in vivo evaluation of a panel of these inhibitors led to identification of 2 (LB42908) as a highly potent (IC(50)=0.9 nM against H-Ras and 2.4 nM against K-Ras) antitumor agent that is currently undergoing preclinical studies.

Alkyl and Aryl Transferases↗
PubMed2001

Branching fraction and photon energy spectrum for b --> s gamma.

We have measured the branching fraction and photon energy spectrum for the radiative penguin process b-->s gamma. We find Beta(b-->s gamma) = (3.21+/-0.43+/-0.27(+0.18)(-0.10))x10(-4), where the errors are statistical, systematic, and from theory corrections. We obtain first and second moments of the photon energy spectrum above 2.0 GeV, = 2.346+/-0.032+/-0.011 GeV, and - (2) = 0.0226+/-0.0066+/-0.0020 GeV(2), where the errors are statistical and systematic. From the first moment, we obtain (in the modified minimal subtraction renormalization scheme, to order 1/M(3)(B) and beta(0)alpha(2)(s)) the heavy quark effective theory parameter Lambda = 0.35+/-0.08+/-0.10 GeV.

Journal Article↗