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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 127 records · Page 7Linked to original sources

Cytologic distinctions between clinical groups using curette-probe compared to cytology brush.

BACKGROUND: We had previously used curette-probe (Rhinoprobe; Arlington Scientific, Springville, UT) to study nasal cytology in various types of patients. Because of the potential sampling ease of using a brush, we sought to compare cytological results obtained with a curette-probe with those obtained using a cytology brush (Cytobrush Plus; Medscand, Malmö, Sweden). OBJECTIVE: To compare the ability of samples of nasal leukocytes obtained with a curette-probe versus a cytology brush to distinguish clinical categories of patients attending an allergy clinic. METHODS: Adult allergy clinic patients were studied by both curette-probe and cytology brush sampling. Quantitation of eosinophils and total leukocytes was performed on samples. Comparisons of cell quantities for each sampling method were made in patients classified into clinical groups. Patients with rhinitis complaints and abnormalities of nasal mucosal appearance with or without aeroallergy were compared with other patients. The adjustment of leukocyte quantities for the numbers of epithelial cells observed was also analyzed. Sampling methods were also compared for receiver operating characteristics. RESULTS: Curette-probe sample leukocyte quantities distinguished patients with symptoms of rhinitis (SR) with abnormal nasal appearance from other patients. This between-group distinction was more significant for leukocyte numbers normalized for the number of epithelial cells. SR patients with both abnormal nasal appearance and aeroallergy had significantly more eosinophils and less goblet cells than other patients. Greater than five curette-probe eosinophils were only observed in patients with SR. Brush samples did not show differences between patients stratified in these ways, and eosinophils were observed in patients without SR. Receiver operating characteristics favored curette-probe samples in terms of leukocyte or eosinophil increases characterizing their respective symptomatic patient subgroups. CONCLUSIONS: Curette-probe-obtained nasal samples allow for leukocyte and eosinophil quantitations which characterize rhinitis patients better than brush-obtained samples. Total leukocyte quantitations obtained by curette-probe may represent a marker of inflammatory nasal disease in adults undergoing allergy evaluation and treatment for rhinitis.

Adult↗

Effects of N-acetylation degree on N-acetylated chitosan hydrolysis with commercially available and modified pectinases.

Three types of N-acetylated chitosans (NACs) with different degrees of acetylation (DA) were prepared and used as a substrate for enzymatic hydrolysis with a commercially available pectinase and a modified one. Pectinase modification was conducted using polyalkyleneoxide-maleic anhydride copolymer (PEO-MA copolymer). The effects of DA on enzymatic reaction with native and modified pectinases were investigated experimentally. Initial hydrolysis rate and Michaelis-Menten kinetic parameters were measured by analysis of reducing sugars. DA of NAC strongly affected the hydrolytic characteristics of native and modified pectinases. N-acetylation of chitosan increased the initial hydrolysis rate and the enzyme-substrate affinity with respect to both pectinases: NACs with DA over 0.3 showed high initial hydrolysis rate and strong affinity between enzyme and substrate. Especially, when NAC with DA over 0.3 was treated with modified pectinase, the affinity became much stronger than the native pectinase.

Journal Article↗

Additional cytotoxic polyacetylenes from the marine sponge Petrosia species.

Ten new polyacetylenic alcohols (1-6, 8-11), along with a known compound, petrocortyne C (7), were isolated from the marine sponge Petrosia sp. The gross structures were established based on NMR and MS data, and the absolute configuration was determined by the modified Mosher's method. These compounds displayed considerable cytotoxicity against a small panel of human solid tumor cell lines. Compounds 1-11 were further evaluated for in vitro inhibitory activity on DNA replication.

Animals↗

The study on the web-based Clinical Database Management System of Oriental Pulse Waveform.

There are many database-oriented sites on the web, which provide basic medical knowledge, hospital information, and medical counseling. However, there are only a few oriental pulse databases on the web. In this perspective, the goal of this study is to develop the Clinical Database Management System of Oriental Pulse Wave Form using the World Wide Web. Accordingly, this study has conducted researches in the Web-based diagnosis data management system of pulse waveform as well as the method of transmitting the data of pulse waveform. In order to set the standard for the documents of the pulse waveform of patients, the web-based clinical database management system has been developed.

Database Management Systems↗

Effect of hypothermia on brain cell membrane function and energy metabolism in experimental Escherichia coli meningitis in the newborn piglet.

We evaluated the anti-inflammatory and neuroprotective effects of hypothermia during the early phase of experimental Escherichia coli meningitis in the newborn piglet. Hypothermia significantly attenuated the meningitis-induced acute inflammatory responses such as increased intracranial pressure, decreased glucose level, increased lactate concentration, increased tumor necrosis factor-alpha level and leukocytosis in the cerebrospinal fluid. Decreased cerebral cortical cell membrane Na+,K+-ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain damage, were significantly improved with hypothermia. Hypothermia also significantly improved the meningitis-induced reduction in brain ATP and phosphocreatine levels. In summary, hypothermia significantly attenuated the acute inflammatory responses and the ensuing brain injury in experimental neonatal bacterial meningitis.

Animals↗

Water-soluble and low molecular weight chitosan-based plasmid DNA delivery.

PURPOSE: Chitosan, a natural cationic polysaccharide, is a candidate non-viral vector for gene delivery because of its high positive charges and low cytotoxicity. In this study, low molecular weight chitosan (LMWC, molecular weight of 22 kDa) was characterized and evaluated as a gene carrier. METHODS: Plasmid/LMWC complex was analyzed in 1% agarose gel electrophoresis. To confirm that the LMWC protected plasmids from nuclease. DNase I protection assays were performed. pSV-beta-galactosidase plasmid/LMWC complex was transfected into 293T cells and transfection efficiency was evaluated by beta-galactosidase assay. Cytotoxicity of LMWC was determined by MTT assay. RESULTS: Unlike high molecular weight chitosan (HMWC), LMWC is highly water soluble, and can form complex with plasmids in physiological buffer. The plasmid DNA was completely retarded at a weight ratio of 1:2 (plasmid:LMWC) in 1% agarose gel. DNase I protection assay showed that plasmids were protected from DNase-I over 60 min. The most efficient transfection was obtained at a weight ratio of 1:3 (plasmid:LMWC). The transfection efficiency of LMWC was significantly higher than naked DNA and higher than poly-L-lysine (PLL). MTT assay showed that LMWC was less cytotoxic than PLL. CONCLUSIONS: LMWC is non-toxic and has higher transfection efficiency than PLL. Therefore, LMWC will be useful in the development of safe gene carriers.

Antineoplastic Agents↗

Design of digital hardware system for pulse signals.

In this study, we have developed the digital hardware system which performs signal processing necessary for the filtering to eliminate noises by inputting pulse wave signals from the sensor group. With a view to obtain clinically effective information, we analyzed structural elements of pulse waveform and, thus, conducted a systematic classification. What is more, we performed the modeling of the digital filter by using the Steiglitz-McBride iteration method in order to get the same results with output signals coming out of an galvanometer of analog type of existing Pulse diagnosis system with input signals entering into galvanometer and coming out of the amp group of the Pulse diagnosis system.

Computers↗

Signalling from the cell surface to the nucleus.

Transcriptional initiation is regulated by altering the properties of promoter-specific DNA-binding proteins, such that these proteins either show altered interaction with the basal transcriptional machinery, or show changes in their cytoplasmic/nuclear distribution. Information is passed from the receptor to the transcription factor by a process of post-translational modifications of pathway components. Post-translational modifications can include phosphorylations or dephosphorylations, which are reversible, and proteolysis, which is irreversible. Specificity within a linear signal transduction pathway is preserved by the existence of scaffold proteins, which serve to co-localize many of the factors from a given linear pathway.

Animals↗

Heart transplant in a factor VIII-deficient patient with a high-titre inhibitor: perioperative management using high-dose continuous infusion factor VIII and recombinant factor VIIa.

Four years prior to transplantation, a 14-year-old boy with severe haemophilia A and a high-responding factor VIII (FVIII) inhibitor developed an anteroseptal myocardial infarct while receiving high doses of an activated prothrombin complex concentrate (PCC). Cardiac transplantation was required for survival because of the ensuing cardiomyopathy. At surgery, the patient's inhibitor titre was 1.8 Bethesda units (BU). High-dose bolus therapy, followed by a continuous infusion of FVIII provided excellent operative and initial postoperative haemostasis without additional blood-product support. Once anamnaesis developed on day 6 postoperatively, recombinant factor VIIa (rFVIIa) therapy was initiated. Haemostasis remained excellent, except for the transient increase in chest-tube bleeding that was noted on day 7. epsilon-Aminocaproic acid was added and haemostasis was re-established. On day 15, rFVIIa was replaced with alternate day infusions of prothrombin complex concentrates (PCCs). On day 21 following the transplant, the patient was discharged, remaining on daily FVIII immune tolerance and thrice-weekly PCC prophylaxis. He remains well 24 months after transplant with an inhibitor titre of 39 BU. This paper describes the second case of cardiac transplantation complicated by haemophilia and an inhibitor, and discusses preoperative planning and operative and postsurgical haemostasis management.

Adolescent↗

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.

Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These molecules are active in both 293 HEK cells and neuronal cultures, and exert their effect upon A beta production without affecting protein secretion, most notably in the secreted forms of the amyloid precursor protein (APP). Oral administration of one of these compounds, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, to mice transgenic for human APP(V717F) reduces brain levels of Ass in a dose-dependent manner within 3 h. These studies represent the first demonstration of a reduction of brain A beta in vivo. Development of such novel functional gamma-secretase inhibitors will enable a clinical examination of the A beta hypothesis that Ass peptide drives the neuropathology observed in Alzheimer's disease.

Administration, Oral↗

Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative damage and antioxidant defences: relevance to Down's syndrome and familial amyotrophic lateral sclerosis.

Patients with Down's syndrome (DS) show elevated levels of copper, zinc-containing superoxide dismutase (SOD1) and appear to have increased lipid peroxidation and oxidative damage to DNA as well as elevated glutathione peroxidase activity. Increasing SOD1 levels by gene transfection in NT-2 and SK-N-MC cell lines also led to a rise in glutathione peroxidase activity, but this was nevertheless accompanied by decreased proliferation rates, increased lipid peroxidation and protein carbonyls, and a trend to a rise in 8-hydroxyguanine and protein-bound 3-nitrotyrosine. Transfection of these cell lines with DNA encoding two mutant SOD1 enzymes (G37R and G85R) associated with familial amyotrophic lateral sclerosis (FALS), produced similar, but more severe changes, i.e. even lower growth rates, higher lipid peroxidation, 3-nitrotyrosine and protein carbonyl levels, decreased GSH levels, raised GSSG levels and higher glutathione peroxidase activities. Since G85R has little SOD activity, these changes cannot be related to increased O(2)(-) scavenging. In no case was SOD2 (mitochondrial Mn-SOD) level altered. Our cellular systems reproduce many of the biochemical changes observed in patients with DS or ALS, and in transgenic mice overexpressing mutant SOD1. They also show the potentially deleterious effects of SOD1 overexpression on cellular proliferation, which may be relevant to abnormal development in DS.

Aldehydes↗

Effect of the overexpression of wild-type or mutant alpha-synuclein on cell susceptibility to insult.

Mutations in alpha-synuclein (A30P and A53T) are involved in some cases of familial Parkinson's disease (FPD), but it is not known how they result in nigral cell death. We examined the effect of alpha-synuclein overexpression on the response of cells to various insults. Wild-type alpha-synuclein and alpha-synuclein mutations associated with FPD were overexpressed in NT-2/D1 and SK-N-MC cells. Overexpression of wild-type alpha-synuclein delayed cell death induced by serum withdrawal or H(2)O(2), but did not delay cell death induced by 1-methyl-4-phenylpyridinium ion (MPP(+)). By contrast, wild-type alpha-synuclein transfectants were sensitive to viability loss induced by staurosporine, lactacystin or 4-hydroxy-2-trans-nonenal (HNE). Decreases in glutathione (GSH) levels were attenuated by wild-type alpha-synuclein after serum deprivation, but were aggravated following lactacystin or staurosporine treatment. Mutant alpha-synucleins increased levels of 8-hydroxyguanine, protein carbonyls, lipid peroxidation and 3-nitrotyrosine, and markedly accelerated cell death in response to all the insults examined. The decrease in GSH levels was enhanced in mutant alpha-synuclein transfectants. The loss of viability induced by toxic insults was by apoptosic mechanism. The presence of abnormal alpha-synucleins in substantia nigra in PD may increase neuronal vulnerability to a range of toxic agents.

1-Methyl-4-phenylpyridinium↗

Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative stress and cell death induced by hydrogen peroxide, 4-hydroxynonenal or serum deprivation: potentiation of injury by ALS-related mutant superoxide dismutases and protection by Bcl-2.

Mutations in Cu/Zn-superoxide dismutase (SOD1) are associated with some cases of familial amyotrophic lateral sclerosis (ALS). We overexpressed Bcl-2, wild-type SOD1 or mutant SOD1s (G37R and G85R) in NT-2 and SK-N-MC cells. Overexpression of Bcl-2 rendered cells more resistant to apoptosis induced by serum withdrawal, H2O2 or 4-hydroxy-2-trans-nonenal (HNE). Overexpression of Bcl-2 had little effect on levels of protein carbonyls, lipid peroxidation, 8-hydroxyguanine (8-OHG) or 3-nitrotyrosine. Serum withdrawal or H2O2 raised levels of protein carbonyls, lipid peroxidation, 8-OHG and 3-nitrotyrosine, changes that were attenuated in cells overexpressing Bcl-2. Overexpression of either SOD1 mutant tended to increase levels of lipid peroxidation, protein carbonyls, and 3-nitrotyrosine and accelerated viability loss induced by serum withdrawal, H2O2 or HNE, accompanied by greater rises in oxidative damage parameters. The effects of mutant SOD1s were attenuated by Bcl-2. By contrast, expression of wild-type SOD1 rendered cells more resistant to loss of viability induced by serum deprivation, HNE or H2O2. The levels of lipid peroxidation in wild-type SOD1 transfectants were elevated. Overexpression of mutant SOD1s makes cells more predisposed to undergo apoptosis in response to several insults. Our cellular systems appear to mimic events in patients with ALS or transgenic mice overexpressing mutant SOD1.

Aldehydes↗

Effective therapy of a vascular tumor of infancy with vincristine.

Vascular tumors are common in infancy, affecting as many as 10% of children. These lesions often follow a benign course, with an initial proliferative phase followed by spontaneous involution, and require no therapy. Others manifest explosive early growth and Kasabach-Merritt phenomenon, requiring therapeutic intervention. Occasionally, some bulky tumors threaten life or vision because of mass effect, also mandating intervention. Steroids are the mainstay of therapy, but often are ineffective. Interferon alpha (2a and 2b) has been used as second-line therapy in cases of steroid failure. However, interferon therapy has been associated with a significant incidence of spastic diplegia. The authors present the case of a 3-month-old girl in whom respiratory distress secondary to tracheal compression developed. Magnetic resonance imaging and magnetic resonance angiography showed a large cervicothoracic lesion encasing the great vessels and displacing the airway. She did not display associated Kasabach-Merritt phenomenon. The lesion proved refractory to standard steroid therapy, but responded dramatically to 4 cycles of vincristine (0.05 mg/kg). Although this agent has been used in children with life-threatening Kasabach-Merritt phenomenon, this is the first time it has been described in the setting of compromised vital function. Vinca alkaloids recently have been shown to have potent antiangiogenic activities in experimental models. Given the low predicted incidence of side effects at this dose, vincristine used as an antiangiogenic agent may prove an attractive alternative therapy for patients with life-threatening vascular tumors of infancy.

Antineoplastic Agents, Phytogenic↗

Contribution of pelvic rotation to lumbar posteroanterior movement.

Variability in lumbar PA stiffness has been found to relate to many factors. Sagittal pelvic rotation has been suggested as one determinant of lumbar PA stiffness. Previous studies have shown that decreased pelvic rotation is associated with increased lumbar PA stiffness. However, it is not known whether variations in pelvic rotation cause changes in PA stiffness. This study aimed to investigate the role of pelvic rotation in determining lumbar PA stiffness, and to investigate whether this role varies with vertebral level of the applied load. A mechanical device was used to apply PA forces to the skin overlying the spinous processes of L2-L5 with the pelvis constrained and unconstrained in 37 subjects without low back pain. Significantly higher PA stiffness (P<0.05) was found when the pelvis was constrained. The degree of increase in PA stiffness depended upon the vertebral level being loaded, with loads at L5 producing the greatest increase in stiffness (24%) and loads at L2 producing a non-significant increase (6%). The findings indicate that sagittal pelvic rotation plays a significant part in the lumbar PA stiffness at L5 but has a lesser influence at more cephalad vertebral levels.

Adult↗

Effect of direction of applied mobilization force on the posteroanterior response in the lumbar spine.

OBJECTIVE: The purpose of this study was to investigate whether changing the direction of applied force affects measured posteroanterior stiffness and associated pelvic (sacral) and lower thoracic rotations. DESIGN: A repeated measures design was used. SETTING: University biomechanical laboratory. PARTICIPANTS: Twenty-four subjects (14 male, 10 female) with no history of recent low back pain or contraindications to mobilization volunteered for testing. MAIN OUTCOME MEASURE: Posteroanterior stiffness was assessed at vertebral levels L3 and L5 through use of 3 sagittal plane directions of applied force; the directions differed by 10 degrees. The amount of sacral and lower thoracic rotation that occurred during loading between 30 and 100 N was also recorded. RESULTS: A small but significant variation of stiffness with direction of applied force was found. At L3, mean stiffness was greatest when the posteroanterior force was applied in a base direction; it was 11% less when the force was applied 10 degrees more caudad than the base direction and 14% less when the force was applied 10 degrees more cephalad than the base direction. There was no significant effect of direction when the force was applied at L5. Both sacral and thoracic rotations displayed significant variation with direction of force when load was applied at L5, with decreasing rotation as the force was applied in a more caudal direction. CONCLUSION: Posteroanterior stiffness in individuals without back pain is affected by the sagittal plane direction in which the posteroanterior force is applied to the lumbar spine. Remote (thoracic and sacral) movements are also affected by the direction of posteroanterior force. Direction of applied force should therefore be controlled, particularly in the research setting.

Adult↗