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Biomedical subjects

E Lee

Publications and source records attributed to E Lee.

At least 199 records · Page 11Linked to original sources
PubMed1998

Systematic development of a block copolymer adjuvant for trivalent influenza virus vaccine.

The current influenza virus vaccines induce systemic humoral immunity and short lived cellular immunity in young adults. Unfortunately these vaccines are only 50% efficacious in the elderly (> 65 years) and high risk groups of the very young. The use of a vaccine adjuvant to correct this deficit would therefore be very beneficial to these population groups. We have developed high molecular weight synthetic non-ionic block copolymers with adjuvant activity. These copolymers are compatible with, and active in, aqueous, physiological formulations in which they spontaneously assemble into 500-3000 nm particles. By varying both the molecular weight and the proportions of hydrophilic and hydrophobic components of the molecule, we have designed the optimal copolymer adjuvant for use with influenza hemagglutinin. This copolymer, termed CRL-1005, was investigated for its ability to augment the immune response of mice to the commercially-available human influenza vaccine, Fluogen. Co-formulation of CRL-1005 with the vaccine resulted in markedly increased antibody titres measured by both ELISA and the functional haemagglutination inhibition assay, indicating that critical immunogen epitopes were not destroyed. A single dose of copolymer and vaccine produced both long term rising antibody titres (six months) and primed for a potent secondary response. This high molecular weight copolymer is non-toxic and should therefore be well suited for widespread use.

Adjuvants, Immunologic↗
PubMed1998

The effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-amino-N-methylsuccinimides.

In connection with the development of new anticonvulsant agents with a broad spectrum, we found that N-Cbz-alpha-amino-N-alkylsuccinimides showed significant anticonvulsant activities, and the pharmacological activities of these compounds were dependent on their stereochemistry and N-substituted alkyl group. These results prompted us to define the effects of other functional group on the anticonvulsant activities of these compounds. Therefore a series of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimide were prepared from N-Cbz-aspartic acid and were evaluated with their anticonvulsant activities against the MES and PTZ tests, in order to define the effect of N-substituted alkoxy carbonyl group with the anticonvulsant activities. From these studies, it was found that all the tested N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides exhibited significant anticonvulsant activities in the PTZ test and were not active in the MES test. The most active compound in the PTZ test was (S) N-ethoxycarbonyl-alpha-amino-N-methyl-succinimide. We found that the pharmacological activities in the PTZ test were dependent on their N-alkoxycarbonyl groups. They follow as such; The order of anticonvulsant activities for (R) series as evaluated by ED50 was N-phenoxycarbonyl = N-4-nitrobenzyloxycarbonyl > N-ethoxycarbonyl > N-allyloxycarbonyl > N-tert. butoxycarbonyl compound; For the (S) series N-ethoxycarbonyl > N-phenoxycarbonyl > N-allyloxycarbonyl compound. From the above results, it was conceivable that N-substituted alkoxycarbonyl group had certain effects on the anticonvulsant activities of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides.

Animals↗
PubMed1998

The effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-aminoglutarimides.

In connection with the development of new anticonvulsant agents with a broad spectrum, we reported that N-Cbz-alpha-aminoglutarimides, combining common structures of other anticonvulsants such as N-CO-C-N and cyclic imides in a single molecule, showed significant anticonvulsant activities in the MES (maximal electroshock seizure) and PTZ (pentylenetetrazole induced seizure) tests. In these studies, a series of (R) and (S) N-alkyloxycarbonyl-alpha-aminoglutarimides 7a-7e and 8a-8e, which were substituted with various alkyloxycarbonyl group instead of Cbz group, were prepared from the corresponding (R) and (S) N-Cbz-glutamic acid 3 and 4, and were evaluated with their anticonvulsant activities against the MES and PTZ tests, including neurotoxicity, in order to define the effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-aminoglutarimides. Among them, (S) N-4-nitrobenzyloxycarbonyl-alpha-amino-N-methylglutarimide 8e was the most active in MES (ED50 = 35.6 mg/kg, PI = 2.7) and PTZ tests (ED50 = 15.6, PI = 6.1). Interestingly, (R) and (S) N-4-nitrobenzyloxycarbonyl-alpha-amino-N-methylglutarimide 7e and 8e and (R) N-phenoxycarbonyl-alpha-amino-N-methylglutrimide 7d showed significant anticonvulsant activities in both the MES and PTZ tests and other compounds showed anticonvulsant activities in only the PTZ test. In addition, it was found that their anticonvulsant activities were dependent on their stereochemistries and N-substituted alkyloxycarbonyl groups.

Animals↗
PubMed1997

Electrophoretic Mobility of a Spherical Particle in a Spherical Cavity.

The electrophoretic mobility U of a spherical particle in a spherical cavity for the case of low electric field is estimated for an arbitrary thick electrical double layer. We show that if the particle is uncharged and the cavity negatively charged, the deviation in the mobility based on the linearized Poisson-Boltzmann equation, UL, can be serious even at a low electrical potential. In this case, the variation of the absolute deviation, |U - UL| as a function of kappaa, kappa and a being, respectively, the reciprocal Debye length and particle radius, has a maximum. The kappaa at which the maximal absolute deviation occurs increases with lambda (particle size/cavity size), and the maximal absolute deviation decreases with lambda. The latter increases with the absolute surface potential of cavity. If the particle is positively charged and the cavity uncharged, UL is sufficiently accurate if the electrical potential is low. Copyright 1997 Academic Press.

Journal Article↗
PubMed1997

Predicting ten-year survival of patients with primary cutaneous melanoma: corroboration of a prognostic model.

BACKGROUND: Recently, the Pigmented Lesion Group at the University of Pennsylvania described a 4-variable model for predicting 10-year survival for patients with primary cutaneous melanoma. The variables are tumor thickness, anatomic site of the lesion, age, and gender. The objective of the current study was to test the validity of this model, employing the large data base of the New York University Melanoma Cooperative Group. METHODS: The predicted probabilities of 10-year survival for 780 patients with primary cutaneous melanoma were determined by multivariate logistic regression, using the 4 variables. RESULTS: The overall 10-year survival rate of the current study group was 78.4%. Of the four variables, tumor thickness, anatomic site of the lesion, and age were found to be independent predictors of survival. Although survival was better for women, gender was not a statistically significant factor in predicting 10-year survival when entered into the multivariate logistic regression model. In the current study, the probability of 10-year survival of patients with melanomas < 0.76 mm ranged from 93-99%, depending on the age and primary site. Age and site had more impact on the prognosis of intermediate and thick melanomas than on thin melanomas. Thus, for melanomas 0.76-1.69 mm, 1.70-3.60 mm, and thicker than 3.60 mm, the probabilities of survival ranged from 70-94%, 39-82%, and 23-68%, respectively. CONCLUSIONS: The wider ranges in survival rates for thicker melanomas, depending on the other variables, emphasize the importance of including variables in addition to tumor thickness in a prognostic model. Using a large data base from a medical center, the current study supports the prognostic multivariate model of the Pigmented Lesions Group of the University of Pennsylvania; however, the authors of the current study did not find gender to be statistically significant in this multivariate model.

Adolescent↗
PubMed1997

Cloning, sequencing and analysis of cDNA encoding bovine intercellular adhesion molecule-1 (ICAM-1).

Intercellular adhesion molecule-1 (ICAM-1) is an inducible glycoprotein that interacts with the leukocyte beta 2-integrins, LFA-1 and Mac-1. We have isolated and analyzed a cDNA clone coding for the putative bovine ICAM-1 gene and compared it with known comparative sequences from other species as well as bovine ICAM-3. The 3398-bp bovine ICAM-1 cDNA sequence codes for 535 amino acids and shows 57% homology with human ICAM-1 and 47% homology with bovine ICAM-3 at the amino acid levels. The predicted number and positions of cysteine residues in bovine ICAM-1 are all conserved among species including bovine ICAM-3. It has two arginine-glycine-aspartate (RGD) sites in the extracellular region and a serine residue in the cytoplasmic tail. Northern blot results show that the bovine ICAM-1 gene is expressed in stimulated leukocytes whereas bovine ICAM-3 is expressed predominantly in resting neutrophils.

Amino Acid Sequence↗
PubMed1997

Changes in actin filament organization during pseudopod formation.

Fluorescent phalloidin has been introduced into Dicytostelium amoebae in order to visualize dynamic changes in the localization of F-actin during pseudopod extension. Phalloidin was initially localized to the peripheral cortex of the cell. Newly formed pseudopods were not fluorescent, indicating that phalloidin was tightly bound to existing F-actin filaments and could not rapidly relocalize to newly formed filaments. As pseudopod extension proceeded, the fluorescent signal disappeared from the region directly underlying the expansion zone, leaving a gap in the actin cortex. Similar results were obtained in both wild-type cells and those lacking myosin II heavy chain. The disappearance of the fluorescent signal from the cortical region underlying the new pseudopod is presumed to be due to breakdown of the actin cortex and dispersion of the remnants. These results suggest that new pseudopods are not built upon the existing actin cortex but rather that the cortex is locally solated as part of the construction of the new actin network.

Actins↗
PubMed1997

Changes in the dengue virus major envelope protein on passaging and their localization on the three-dimensional structure of the protein.

To help define the molecular events involved in dengue virus adaptation during serial passage in vivo and in cultured cells, we have sequenced the structural protein genes of three dengue type 3 isolates after intracerebral passage in mice and after passage in cultured monkey kidney (Vero) and Aedes albopictus (mosquito) cells. Passaging in each host selected for amino acid changes in the envelope protein E and occasionally in prM but not in the capsid protein. Most changes were first apparent within five passages. Nineteen of twenty mutations in the structural protein genes resulted in amino acid changes concentrated on 12 residues; 9 of the 12 amino acid changes were at residues which are conserved between the four dengue virus serotypes. Certain amino acid changes were repeatedly selected on passage in cell culture. In six independent Vero cell passage series, changes were observed in E at residues 191 (four times), 202 (twice), 266 and 268 (three times), and 291; change in prM was seen in two passage series at residue 26. Two independent passage series in mosquito cells each resulted in the loss of a conserved glycosylation site at Asn 153 in E. Passage in mouse brain selected for mutations at E residues 18, 54, 277, 401, and 403. Residues which altered on passaging have been localized on the three-dimensional structure of the tick-borne encephalitis virus E protein soluble fragment (F. A. Rey, et al., 1995, Nature 375, 291-298). Residues 54, 191, 202, 266, 268, and 277 map to a postulated "hinge" region between domains I and II which may be involved in fusion of flaviviruses with cell membranes. The oligosaccharide at Asn 153 also appears to be involved in flavivirus fusion. Changes in the fusion characteristics of the passaged viruses were demonstrated.

Aedes↗
PubMed1997

Cervical sagittal range-of-motion analysis using three methods. Cervical range-of-motion device, 3space, and radiography.

STUDY DESIGN: Cervical flexion, extension, protrusion, and retraction were comparatively measured in volunteers using a cervical range-of-motion device (Performance Attainment Associates, Roseville, MN), a 3space system (Polhemus, Colchester, VT), and lateral radiographs. OBJECTIVES: To compare the outcomes of three methods of measurement of cervical flexion, extension, protrusion, and retraction. SUMMARY OF BACKGROUND DATA: Few studies compare cervical range-of-motion measurement devices with radiographic measurements, and no studies have compared methods of measurement for cervical protrusion and retraction measurement. METHODS: In 20 asymptomatic volunteers, four end-range sagittal cervical positions (flexion, extension, protrusion, and retraction) were measured simultaneously using a cervical range-of-motion device, a 3Space and lateral cervical radiographs. Measurements were compared, and differences were analyzed. RESULTS: There were no significant differences for flexion and extension measurements between the cervical range-of-motion device and that radiographic angle determined by an occipital line and the vertical, nor were there any between the 3Space and that radiographic angle between this same occipital line and C7. The cervical range-of-motion device and the 3Space measurements for flexion and extension, however, differed significantly from one another (P < 0.05). For protrusion and retraction, there was no significant difference between the 3Space and radiographic measurements, but these two both differed significantly from the cervical range-of-motion device (P < 0.05). CONCLUSIONS: Available methods of measurement differ as to whether the cervical spine is isolated or includes upper thoracic motion. Protrusion and retraction can be measured reliably with all three methods studied, but without measurement consistency between devices. Because end-range cervical flexion and extension-cannot occur in isolation from upper thoracic motion, true cervical motion can be measured only with an internally referenced, or landmark-based, methodology such as the 3Space. Even though the cervical range-of-motion device cannot measure isolated cervical flexion and extension, it is nevertheless a reliable clinical tool in measuring flexion and extension as well as protrusion and retraction as long as patient thoracic positioning is standardized to minimize the upper thoracic contribution.

Adult↗
PubMed1997

Time to treatment with thrombolytic therapy: determinants and effect on short-term nonfatal outcomes of acute myocardial infarction. Canadian GUSTO Investigators. Global Utilization of Streptokinase and + PA for Occluded Coronary Arteries.

OBJECTIVES: To characterize the extent of delay in administration of thrombolytic therapy to patients with acute myocardial infarction (AMI) in Canada, to examine patient-specific predictors of such delay and to measure the effect of delay on short-term nonfatal cardiac outcomes. DESIGN: Secondary cohort analysis of data from the first international Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO-I) trial. SETTING: Sixty-three acute care hospitals across Canada. SUBJECTS: All 2898 Canadian patients with an AMI enrolled in GUSTO-I. MAIN OUTCOMES: Time before arrival at a hospital ("symptom-to-door" time) and time from arrival to administration of therapy ("door-to-needle" time) for patients who had an AMI outside of a hospital, in clinically relevant categories; proportions of patients with nonfatal, serious cardiac events, including shock, sustained ventricular tachycardia, ventricular fibrillation and asystole. RESULTS: Of the total number of patients enrolled, records were complete for 2708; 2542 of these patients (93.9%) had an AMI outside of a hospital. These 2542 patients presented a median 81 (interquartile range 50 to 130) minutes after the onset of symptoms, and the median time to treatment in hospital was 85 (interquartile range 61 to 115) minutes. Whereas a greater proportion of Canadian patients than of patients enrolled in GUSTO-I in other countries reached hospital within 2 hours of symptom onset (71.5% v. 61.2%, p < 0.001), a greater proportion of Canadian patients experienced in-hospital treatment delays of more than 1 hour (75.3% v. 57.1%, p < 0.001). In an analysis of all 2708 patients with complete records, both the unadjusted and adjusted odds of nonfatal cardiac events for those treated 4 to 6 hours after symptom onset were significantly higher than for those treated within 2 hours (odds ratio 1.60, 95% confidence interval 1.09 to 2.37). CONCLUSION: After arrival at a hospital, Canadian patients enrolled in GUSTO-I received thrombolytic therapy more slowly than trial enrollees in other countries. Such delays are already known to decrease the rate of short-term survival after AMI. The findings further show that long time to treatment also increases the odds of nonfatal, serious cardiac events. Hospitals and physicians caring for patients with AMI should routinely assess whether and how they can improve door-to-needle times.

Adult↗
PubMed1997

Nucleotide sequence of the Barmah Forest virus genome.

Barmah Forest virus (BFV) is an atypical alphavirus [Dalgarno, L., Short, N. J., Hardy, C. M., Bell, J. R., Strauss, J. H., and Marshall, I. D. (1984). Virology 133, 416-426] and has been classified as the sole known member of a seventh alphavirus serocomplex. The complete nucleotide sequence of BFV genomic RNA is 11,488 nucleotides in length excluding the poly(A) tail. Two long open reading frames in the RNA encode a nonstructural polyprotein of 2411 amino acids and a structural polyprotein of 1239 amino acids, respectively. The BFV envelope protein E2 is unique among sequenced alphaviruses in having no N-linked glycosylation sites; E1 carries two glycosylation sites. From amino acid sequence comparisons with sequenced alphaviruses BFV is most closely related to Ross River and Semliki Forest viruses. Sequence homology between BFV and other alphaviruses is relatively uniform along the length of the nonstructural and structural polyproteins, providing no evidence that BFV has arisen from recombination between ancestral alphaviruses in the coding region of the genome. The BFV 3' noncoding region of 445 nucleotides has unusual features. There are two unrelated sequence blocks of 48 nucleotides (sequence I) and 47 nucleotides (sequence II) both of which are repeated once. Sequence I is closely related to a repeat in the 3' noncoding region of Ross River and Getah viruses; sequence II is unrelated to repeat blocks in other sequenced alphaviruses. Thus, recombination between ancestral viruses may have played a role in the evolution of the BFV 3' noncoding region.

Alphavirus↗
PubMed1997

Efficiency and productivity of a sheathed fiberoptic sigmoidoscope compared with a conventional sigmoidoscope.

PURPOSE: The aim of this study was to measure and compare time and productivity between a new sheathed flexible sigmoidoscope and a traditional fiberoptic flexible sigmoidoscope relative to labor and cost analysis. METHODS: Two flexible sigmoidoscopes, the Vision Sciences sigmoidoscope using a protective sheath covering requiring removal and replacement between procedures and a conventional flexible sigmoidoscope requiring meticulous cleaning using a washer and high-level disinfection, were compared. Sigmoidoscope preparation was defined as the average time between the procedures (reprocessing, start to finish) and was measured by an independent nonmedical timekeeper JG). The parameter recorded was scope reprocessing time. RESULTS: Ten procedures were performed using the sheathed flexible sigmoidoscope system compared with nine using a conventional sigmoidoscope. Scope performance and endoscopic visualization for both systems were comparable. The average reprocessing time was 46.8 minutes for the conventional sigmoidoscope vs. 4.9 minutes for the sheathed sigmoidoscope (P < 0.0001). The average time saved was 9.5 times greater with the sheathed flexible sigmoidoscope system than with the conventional sigmoidoscope. CONCLUSION: The almost tenfold difference in the time saved using the sheathed flexible sigmoidoscope system represents increased productivity and potentially decreased overall labor cost. By reducing endoscope turnover time, this new sheathed system can reduce or even eliminate the need for backup endoscopes and endoscope washers and potentially allow better use of nursing staff.

Endoscopes↗
PubMed1997

Molecular analysis of the adenomatous polyposis coli gene in sarcomas, hematological malignancies and noncolonic, neoplastic tissues.

Somatic mutations of the adenomatous polyposis coli (APC) gene have been frequently found in sporadic colorectal tumors, and the frequency of such mutations remain constant as tumors progress from benign adenomas to malignant cancers. Thus the mutations of the APC gene may have a major role in the early development of sporadic colorectal tumors. Whether inactivation of the APC gene accounts for other types of primary tumors is still being investigated. We investigated for APC mutations within the mutation cluster region (a 684-bp region containing most of the mutations found in colorectal tumors) in 317 samples from a wide variety of human malignant and premalignant tissues, including 40 lung cancers, 47 renal cell carcinomas, 41 osteosarcomas and 21 other types of sarcomas, 45 acute lymphoid leukemias/lymphomas, 33 acute myeloid leukemias, 27 myelodysplastic syndrome samples, and 20 chronic colitis (ulcerative colitis and Crohn's disease) associated cancers and dysplasias, and 43 human malignant cell lines. We used single-strand conformation polymorphism assay following polymerase chain reaction. Samples with abnormal assay results were reamplified and analyzed by the direct DNA sequencing method. We detected a total of two cases with a base substitution. A silent mutation was detected in a case of myelodysplastic syndrome, and a novel nonsense mutation was discovered in a colorectal cancer cell line, SW837. In summary, we did not detect any functional mutations of the APC gene in a wide variety of tumors except for a colon cancer cell line, suggesting that alterations of the APC gene do not have a major role in the development of lung and renal cancers, various types of sarcomas, or hematological malignancies.

Colonic Neoplasms↗
PubMed1997

Impaired early growth of infants perinatally infected with human immunodeficiency virus: correlation with viral load.

OBJECTIVE: To evaluate the effect of viral load on the early growth of infants infected with human immunodeficiency virus (HIV). METHODS: Plasma concentrations of p24-antigen and HIV ribonucleic acid were measured retrospectively and correlated with growth parameters for the first 18 months of life in a cohort of 47 term infants born to HIV-infected mothers prospectively enrolled in a study of perinatal HIV transmission. Comparisons of the mean weight and length of the 18 HIV-infected and 29 uninfected infants for each interval and across intervals were made. Viral load was correlated with standard deviation scores. Infants were stratified by high and low viral load during the first 6 months of life. RESULTS: At birth, no difference in weight and length was observed between HIV-infected and uninfected infants. Between birth and 6 months of age, the infected infants grew less rapidly than the uninfected infants, a finding temporally associated with an exponential increase in HIV viremia. The linear growth of infected infants remained consistently less than that of the uninfected infants after 6 months of life, although the differences were no longer statistically significant and tended to decrease with age in parallel with declines in viral load. The median plasma concentration of HIV ribonucleic acid was significantly higher at 3, 6, 12, and 18 months in infected infants in whom growth failure developed. Infants who had a high viral load in the first 6 months of life were significantly more likely to have severe growth failure. Though the mean SD for weight of the infected infants was always less than that of the uninfected infants, the differences were small and not significant. CONCLUSIONS: Our results confirm the observation that stunting is an early frequent finding in perinatal HIV infection. The deleterious effect of HIV on linear growth appears to be correlated with the level of postnatal HIV viremia, although the exact mechanism of this association remains to be elucidated.

Birth Weight↗
PubMed1997

Molecular characterization of the inhibitory myotropic peptide leucomyosuppressin.

The myoinhibitory peptide leucomyosuppressin (LMS) (pQDVDHVFLRFamide) has been identified and characterized at the molecular level in the cockroach Diploptera punctata through analysis of the organization of both brain cDNA and genomic DNA. Processing of the precursor predicted from DNA sequence would release a single LMS peptide. The organization of the precursor appears to be conserved in other insects and may reflect a functional organization for this subfamily of extended FLRFamides. The expression of the LMS gene appears in numerous cells of the pars-intercerebralis of the cockroach protocerebellum as well as in numerous endocrine cells of the midgut.

Alternative Splicing↗