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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 253 records · Page 14Linked to original sources
PubMed2001

Permeabilization and recovery of the stratum corneum in vivo: the synergy of photomechanical waves and sodium lauryl sulfate.

BACKGROUND AND OBJECTIVE: Photomechanical waves render the stratum corneum permeable and allow macromolecules to diffuse into the epidermis and dermis. The aim of this study was to investigate the combined action of photomechanical waves and sodium lauryl sulfate, an anionic surfactant, for transdermal delivery. STUDY DESIGN/MATERIALS AND METHODS: A single photomechanical wave was applied to the skin of rats in the presence of sodium lauryl sulfate. The sodium lauryl sulfate solution was removed and aqueous solutions of rhodamine-B dextran (40 kDa molecular weight) were applied to the skin at time points 2, 30, and 60 minutes post-exposure. The presence of rhodamine-B dextran in the skin was measured by fluorescence emission spectroscopy in vivo and fluorescence microscopy of frozen biopsies. RESULTS: The use of sodium lauryl sulfate delayed the recovery of the stratum corneum barrier and extended the time available for the diffusion of dextran through it. CONCLUSION: The combination of photomechanical waves and surfactants can enhance transdermal drug delivery.

Administration, Cutaneous↗
PubMed2001

Syngeneic consecutive rat spleen transplantation bearing infantile testis.

Seventy-seven Lewis adult rats received autologous testicular implants in the spleen. These spleens were retransplanted in a consecutive transplant fashion as we described earlier. Some were observed as long as 26 to 27 months. Although earlier splenic-testicular transplants showed benign granulosa cell tumors, some of the long-term follow-ups showed a seminoma-like transformation.

Animals↗
PubMed2001

The biosynthesis of acarbose and validamycin.

The studies reported here have established the biosynthetic origin of the mC7N units of acarbose and validamycin from sedo-heptulose 7-phosphate, and have identified 2-epi-5-epi-valiolone as the initial cyclization product. The deoxyhexose moiety of acarbose arises from glucose with deoxythymidyl-diphospho-4-keto-6-deoxy-D-glucose (dTDP-4-keto-6-deoxy-D-glucose) as a proximate intermediate. However, despite the identical origin of the aminocyclitol moieties in acarbose and validamycin A, the pathways of their formation seem to be substantially different. Validamycin A formation involves a number of discrete ketocyclitol intermediates, 5-epi-valiolone, valienone, and validone, whereas no free intermediates have been identified on the pathway from 2-epi-5-epi-valiolone to the pseudodisaccharide moiety of acarbose. The stage is now set for unraveling the mechanism or mechanisms by which the two components of the pseudodisaccharide moieties of acarbose and validamycin are uniquely coupled to each other via a nitrogen bridge.

Acarbose↗
PubMed2001

Spontaneous inflammatory disease in HLA-B27 transgenic mice does not require transporter of antigenic peptides.

HLA-B27 is strongly linked with a group of human diseases called spondyloarthropathies. Even though HLA-B27 as an MHC class I molecule would be expected to present endogenously processed peptides such as cytosolic or viral proteins, many of the B27-linked diseases begin after an infection with an enterobacteria, an exogenous antigen. In our previous studies, we have described development of spontaneous inflammatory disease in HLA-B27 transgenic mice expressing beta(2)m free heavy chains on the cell surface. In order to address the role of endogenous versus exogenous antigens and a role for Tap genes in the development of spontaneous diseases, mice lacking Tap-1 (knockout) were mated to HLA-B27/human beta(2)m transgenic mice. B27(+)/human beta(2)m(+) double-transgenic mice (without mouse beta(2)m) lacking the Tap-1 gene developed spontaneous inflammatory disease similar to wild-type Tap-1 gene-expressing counterparts. Our data demonstrate that peptide transporters (Tap) were not involved in the development of spontaneous inflammatory disease in B27(+)/human beta(2)m transgenic animals.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

The pattern of gene expression in mouse Gr-1(+) myeloid progenitor cells.

To understand the pattern of gene expression in mouse myeloid progenitor cells, we carried out a genome-wide analysis of gene expression in mouse bone marrow Gr-1(+) cells using SAGE and GLGI techniques. We identified 22,033 unique SAGE tags with quantitative information from 73,869 collected SAGE tags. Among these unique tags, 64% match known sequences, including many genes important for myeloid differentiation, and 36% have no matches to known sequences and are likely to represent novel genes. We compared the expression of mouse Gr-1(+) and human CD15(+) myeloid progenitor cells and showed that the pattern of gene expression of these two cell populations had some similarities. We also compared the expression of mouse Gr-1(+) myeloid progenitor cells with that of mouse brain tissue and found a highly tissue-specific manner of gene expression in these two samples. Our data provide a basis for studying altered gene expression in myeloid disorders using mouse models.

Animals↗
PubMed2001

Characteristics and survival of cervical cancer patients managed at adjacent urban public and university medical centers.

OBJECTIVE: The goal of this work was to compare characteristics and survival of cervical cancer patients at adjacent public and university hospitals to define the effects of poverty and ethnicity on disease. METHODS: A retrospective chart review was conducted of cervical cancer patients managed by gynecologic oncologists at two adjacent urban hospitals between 1992 and 1998. Continuous variables were compared by t test, categorical variables by chi(2), and survival by the Kaplan-Meier and log-rank methods. RESULTS: In all, 372 patients were identified, with 209 (56%) at the public hospital and 163 (44%) at the adjacent university hospital. Ethnic distribution differed between the two hospitals: 100 (52%) versus 46 (28%) African-American, 56 (29%) versus 13 (8%) Hispanic, 31 (16%) versus 96 (60%) Caucasian, and 5 (3%) versus 6 (4%) other (P < 0.001). In addition, public hospital patients presented with more advanced cancers (stages II--IV) than those managed at the university hospital, 96 (48%) versus 53 (34%) (P = 0.008), and squamous cancers were more common at the public hospital, 154 (89%) versus 120 (76%) (P = 0.03). However, with a median follow-up of 17 months, stage-adjusted survival did not differ between the two institutions. CONCLUSIONS: The higher proportions of advanced and squamous cervical cancers encountered at the public hospital likely reflect suboptimal screening. Equal access to gynecologic oncologists eliminated disparities in stage-adjusted survival. Efforts at earlier diagnosis should be directed at indigent, especially minority women.

Adult↗
PubMed2001

Compliance with and acute hematologic toxic effects of chemoradiation in indigent women with cervical cancer.

OBJECTIVES: The goals of this work were to describe the compliance with and acute hematologic toxic effects of chemoradiation for cervical cancer in indigent women and to explore the likelihood that chemoradiation is effective outside research settings. We hypothesized that if compliance and toxicity are not limiting in this high-risk group of patients, the effectiveness of chemoradiation for cervical cancer in community settings is likely to mirror the efficacy demonstrated in clinical trials. METHODS: This study is a retrospective review of prospectively maintained data on women with newly diagnosed cervical cancer treated with chemoradiation between August 1998 and August 2000. Cisplatin was given weekly at 40 mg/m(2) to a maximum of six courses. A WBC count <3000/mm(3) resulted in cancellation of cisplatin but not radiation, and patients were transfused for hemoglobin <9 g/dl. Statistical analysis was performed using the t test, chi(2) test, and Fisher's exact test. RESULTS: In all, 19 of 65 patients treated (29.2%) missed at least one chemotherapy cycle, with 10 (15.4%) due to missed appointments, 8 (12.3%) due to a low WBC count, and 1 due to increased creatinine. Nineteen patients (29.2%) received RBC transfusion during chemoradiation, and two (3%) had platelets <75,000/mm(3). Noncompliant patients had a lower mean total point A dose (7986 cGy vs 8413 cGy, P = 0.04) and longer overall treatment duration (79 days vs 51 days, P < 0.001). No patient had a fatal hematologic complication. CONCLUSION: Nearly a third of the indigent women treated with chemoradiation for cervical cancer do not complete the prescribed treatment, and a similar number require blood transfusions. In indigent and minority women, the effectiveness of chemoradiation protocols may not mirror the efficacy obtained in clinical trials.

Adult↗
PubMed2001

One micrometer resolution NMR microscopy.

We obtained a magnetic resonance image of 1 microm resolution and 75 microm(3) voxel volume for a phantom filled with hydrocarbon oil within an hour at 14.1 T. For this work, a specially designed probe with a high sensitivity RF coil and gradient coils generating over 1000 G/cm was built. The optimal pulse sequence was analyzed in consideration of the bandwidth, diffusion coefficients, and T(1) and T(2) relaxations of the medium. The system was applied to the in vivo imaging of a geranium leaf stem to get the images of 2 microm resolution and 200 microm(3) voxel volume.

Magnetic Resonance Spectroscopy↗
PubMed2001

A MILP-based flux alternative generation and NMR experimental design strategy for metabolic engineering.

A mixed-integer linear program (MILP) is described that can enumerate all the ways fluxes can distribute in a metabolic network while still satisfying the same constraints and objective function. The multiple solutions can be used to (1) generate alternative flux scenarios that can account for limited experimental observations, (2) forecast the potential responses to mutation (e.g., new reaction pathways may be used), and (3) (as illustrated) design (13)C NMR experiments such that different potential flux patterns in a mutant can be distinguished. The experimental design is enabled by using the MILP results as an input to an isotopomer mapping matrices (IMM)-based program, which accounts for the network circulation of (13)C from a precursor such as glucose. The IMM-based program can interface to common plotting programs with the result that the user is provided with predicted NMR spectra that are complete with splittings and Lorentzian line-shape features. The example considered is the trafficking of carbon in an Escherichia coli mutant, which has pyruvate kinase activity deleted for the purpose of eliminating acetate production. Similar yields and extracellular measurements would be manifested by the flux alternatives. The MILP-IMM results suggest how NMR experiments can be designed such that the spectra of glutamate for two flux distribution scenarios differ significantly.

Algorithms↗
PubMed2001

A new naphthoquinone from Pyrola japonica.

A new naphthoquinone, 5,8-dihydro-2,7-dimethyl-[1,4]naphthoquinone (1), which was named 5,8-dihydrochimaphilin, isolated from an ethyl acetate soluble fraction from the root of Pyrola japonica, together with chimaphilin (2). Compound 1 was transformed rapidly to 2 upon exposure to air by HPLC analysis. This fact supported that chimaphilin (2) may be an artifact from 1.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Cytotoxic triterpenoides from Alismatis Rhizoma.

Four prostane-type triterpenes were isolated from a methanol extract of Alismatis Rhizoma by bioassay-guided isolation using in vitro cytotoxic assay. The compounds were identified as alisol B 23-acetate (1), alisol C 23-acetate (2), alisol B (3), alisol A 24-acetate (4) by spectroscopic methods. Amongst the compounds, alisol B (3) showed significant cytotoxicity against SK-OV3, B16-F10, and HT1080 cancer cell lines with ED50 values of 7.5, 7.5, 4.9 microg/ml, respectively.

Animals↗
PubMed2001

Vitamin D status of an outpatient clinic population.

Vitamin D insufficiency contributes to bone loss and fracture risk. Low 25-hydroxyvitamin D (25OHD) levels are common in elderly people and in housebound and hospitalized patients. This study was conducted to assess wintertime 25OHD levels in relation to self-reported vitamin D supplement use in an outpatient thyroid clinic population. We assessed the medical history, vitamin D intake from milk and supplements, and serum 25OHD levels in 231 women and 41 men who attended a Thyroid Clinic between January and March, 1999. Of the 272 outpatients, 13.6% had 25OHD levels <40 nmol/l and 53.3% had levels below 80 nmol/l. Fewer than 15% of the patients consumed more than 200 IU per day of vitamin D from milk. Vitamin D supplement use was a positive determinant of serum 25OHD concentration (P < 0.001). For example, among the largest homogenous subset of patients, Caucasian women (n = 137), 30% of the unsupplemented women, and 65% of those taking 400 lU/day of vitamin D had levels of 25OHD as high as 80 nmol/l. Other significant determinants of 25OHD levels were race, weight, milk intake, and recent southern travel. Thyroid disorder, serum TSH level, and age were not predictors of serum 25OHD concentration. In conclusion, at their current dietary vitamin D intake levels, most patients at this latitude will need vitamin D supplements in the wintertime.

Adult↗
PubMed2001

Control of stromal keratitis by inhibition of neovascularization.

Stromal keratitis resulting from ocular infection with herpes simplex virus is a common cause of blindness. This report investigates the role of neovascularization in the pathogenesis of stromal keratitis by measuring the outcome of treatment with the potent anti-angiogenesis cytokine endothelial monocyte-activating polypeptide II (EMAP II). We show that systemic and topical administration of EMAP II from the outset of infection resulted in markedly diminished levels of herpes simplex virus-induced angiogenesis and significantly reduced the severity of stromal keratitis lesions. EMAP II treatment had no demonstrable pro-inflammatory or toxic effects and failed to express antiviral activity. The mechanism of action of EMAP II was shown to proceed by causing apoptosis in vascular endothelial cells. Our data document for the first time the essential role of angiogenesis in the pathogenesis of stromal keratitis and also indicate that the therapy of herpetic stromal keratitis could benefit by procedures that diminish angiogenesis.

Angiogenesis Inhibitors↗
PubMed2001

Analysis of residual saliva and minor salivary gland secretions.

Residual saliva and minor salivary gland secretions are important for the maintenance of oral mucosal wetness. Salivary proteins and glycoproteins are the major components of the oral mucosal film, which functions as a moisture retainer and a protective barrier. Here, the correlations between the amounts of residual saliva and minor salivary gland secretions and their protein concentrations were investigated in 30 normal healthy individuals. The thickness of the mucosal film was measured at six mucosal surfaces and minor salivary gland secretion rate was measured at two mucosal surfaces. The thickness of residual saliva was determined by placing filter-paper strips against the mucosa at each site for 5 s and then measuring the volume electronically with a Periotron 8000 micro-moisture meter. The unstimulated rate of minor salivary gland secretion was measured for 30 s by the same method. Unstimulated whole salivary flow rate was measured with the spitting method. The total protein concentration of all salivary samples was measured by bicinchoninic acid assay. Before the experiment, the intra-/inter-examiner reliability of the method using the Periotron and the filter-paper strips was investigated. With a range of 0.4256-0.8846, the intraclass correlation coefficient, measured within and between examiners, was indicative of good reliability. The oral mucosal site with the thinnest coat of residual saliva was the anterior hard palate. Mucosal wetness on the hard palate and buccal mucosa showed significant positive correlations with the unstimulated whole salivary flow rate and significant negative correlations with the total protein concentration of residual saliva. Mucosal wetness on the upper and lower labial mucosa also showed significant negative correlations with the total protein concentration of residual saliva. Mucosal wetness on the soft palate was correlated with the minor salivary gland secretion rate (r=0.477, P<0.01). Among the minor salivary glands, the secretion rate of soft palate glands in females showed a significant correlation with the unstimulated whole salivary flow rate (r=0.563, P<0.05) and a significant negative correlation with its total protein concentration (r=-0.525, P<0.05). These data suggested that oral mucosal wetness and minor salivary gland secretions could be influenced by various factors differently according to mucosal sites.

Adult↗
PubMed2001

Progressive rearrangement of subtilisin Carlsberg into orderly and inflexible conformation with Ca(2+) binding.

Fluorescence depolarization and decay kinetic profiles, together with differential scanning calorimetric thermograms and circular dichroism spectra, are measured to understand the respective roles of Ca(2+) ions at the strong (Ca1) and weak binding sites (Ca2) of subtilisin Carlsberg (sC). Thermal denaturation temperature decreases considerably with Ca1 removal, whereas it does slightly with Ca2 removal. The fraction of random coil structure increases significantly with Ca2 removal as well as with Ca1 removal. sC shows three fluorescence decay times of 100, 1100, and 3300 ps. Although the fast and the slow do not change noticeably, the medium one decreases progressively with Ca(2+) removal. sC has two fluorescence anisotropic decay components of 340 and 12,000 ps. The fast one arises from the internal rotation of Tyr, whereas the slow results from the global rotation of sC. Although both become significantly faster with Ca2 removal, only the slow one becomes slightly faster with further Ca1 removal. Overall, sC undergoes progressive rearrangement into disorderly and flexible conformation with Ca(2+) removal, indicating that both Ca1 and Ca2 are indispensable for the stable structure of sC.

Binding Sites↗
PubMed2001

Combined angiotensin converting enzyme inhibition and angiotensin AT(1) receptor blockade up-regulates myocardial AT(2) receptors in remodeled myocardium post-infarction.

OBJECTIVES: In an ovine model of left ventricular (LV) remodeling after transmural anteroapical myocardial infarction (MI), we have previously demonstrated that the combination of angiotensin converting enzyme (ACE) inhibition and AT(1) receptor blockade is more effective at limiting LV remodeling than either therapy alone. We hypothesized that the beneficial effect of combined therapy is due in part to upregulation of AT(2) receptor levels. METHODS: Two days after transmural anteroapical MI by coronary ligation, 16 sheep were randomized to losartan (50 mg/day), ramipril (10 mg/day), ramipril+losartan (combined therapy), or no therapy. At 8 weeks after MI, radioligand receptor assay were deployed with homogenates from regional LV tissues. RESULTS: We found that AT receptors in normal sheep myocardium are predominantly of the AT(2) receptor subtype. Binding studies of remodeled myocardium 8 weeks later showed that the apparent maximum binding (B(max)) was increased from 23 to 48 fmol/mg protein only in animals with combined therapy. The AT(2)/AT(1) proportion was increased significantly in animals with combined therapy compared to infarcted controls (18.0 vs. 5.17). CONCLUSIONS: These results indicate that AT(2) receptor expression increased significantly during LV remodeling with combined therapy but not with either therapy alone. In combination with prior work demonstrating the effectiveness of combined therapy in limiting LV remodeling, this study is consistent with the hypothesis that AT(2) receptors play a cardioprotective role in LV remodeling after MI.

Analysis of Variance↗
PubMed2001

STATT: a titrate-to-goal study of simvastatin in Asian patients with coronary heart disease. Simvastatin Treats Asians to Target.

BACKGROUND: Most published studies on the use of lipid-lowering agents to treat hypercholesterolemia have focused on Western populations, with few data on Asian populations. OBJECTIVE: The Simvastatin Treats Asians to Target (STATT) study used a titrate-to-goal protocol to evaluate the efficacy and tolerability of simvastatin 20 to 80 mg/d in the treatment of Asian patients with coronary heart disease. METHODS: This was a multicenter, open-label, uncontrolled, 14-week study in patients with coronary heart disease and serum low-density lipoprotein cholesterol (LDL-C) levels of 115-180 mg/dL and triglyceride levels of < or = 400 mg/dL. The dose of simvastatin was titrated from 20 to 80 mg/d to achieve the National Cholesterol Education Program (NCEP) LDL-C target of < or = 100 mg/dL. The primary efficacy measure was the percentage of patients achieving the NCEP target. Among secondary measures were the percentage of patients achieving European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension target LDL-C levels of < or = 115 mg/dL and the percentage change from baseline in lipid parameters. Tolerability was assessed in terms of the overall incidence of adverse experiences and the incidences of the most commonly reported adverse experiences. RESULTS: The intent-to-treat analysis included 133 Asian patients (93 men, 40 women; mean age, 59.5 years), of whom 125 completed 14 weeks of therapy. Their mean blood pressure was 130.2/79.4 mm Hg. Overall, 104 (78.2%) patients treated with simvastatin achieved LDL-C levels < or = 100 mg/dL at week 14, and 125 (94.0%) achieved this target at some point during the study. Similarly, 122 (91.7%) patients achieved an LDL-C level < or = 115 mg/dL at week 14, and 130 (97.7%) achieved this target at some point during the study. Treatment with simvastatin had favorable effects on the lipid profile, producing significant percentage changes from baseline in all parameters (P < 0.001). Simvastatin was well tolerated across the dose range. Overall, 40 patients (30.1%) had > or = 1 clinical adverse experience. Only 14 (10.5%) had adverse experiences that were possibly, probably, or definitely related to study drug; none of these experiences were considered serious. The most common adverse experiences (> or = 3% incidence) were abdominal pain (6%); chest pain (5%); dizziness (4%); and asthenia/fatigue, fibromyalgia, headache, insomnia, and upper respiratory tract infection (3% each). No new or unexpected adverse experiences were seen at the higher doses. CONCLUSIONS: Simvastatin was effective and well tolerated at doses of 20, 40, and 80 mg/d in Asian patients with coronary heart disease. Titration enabled the majority to achieve target LDL-C levels of < or = 100 mg/dL.

Aged↗