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Biomedical subjects

S M Lee

Publications and source records attributed to S M Lee.

At least 91 records · Page 5Linked to original sources

Effects of huangqi jianzhong tang on hematological and biochemical parameters in judo athletes.

AIM: The purpose of the study was to investigate the effects of Huangqi Jianzhong Tang (HQJZT) on hematological and biochemical parameters in judo athletes. METHODS: Sixteen male and eight female judo athletes in Hsin-Ming senior high school were randomly and stratified divided into control and experimental group, which received placebo and HQJZT respectively during the five-week training program. The measurement of the hematological and biochemical parameters was performed twice, just before and after the training. The data was analyzed with paired-t test and ANOVA. RESULTS: The values of RBC, Hb, and Hct were obvious decreased after intervention, while the value of GOT, GPT, BUN, and CK was elevated. CONCLUSION: The results indicated the hematological and biochemical changes were caused by the physical training but not the effects of HQJZT. The HQJZT had no adverse effects on the judo athletes in our study.

Adolescent↗

Mechanism-based discovery of ligands that counteract inhibition of the nicotinic acetylcholine receptor by cocaine and MK-801.

Nicotinic acetylcholine receptors (AChR) belong to a family of proteins that form ligand-gated transmembrane ion channels. They are involved in the fast transmission of signals between cells and the control of intercellular communication in the nervous system. A variety of therapeutic agents and abused drugs, including cocaine, inhibit the AChR and monoamine transporters and interfere with nervous system function. Here we describe a mechanism-based approach to prevent this inhibition. We had previously developed presteady-state kinetic (transient kinetic) techniques, with microsecond-to-millisecond time resolutions, for investigations of reactions on cell surfaces that allow one to determine the effects of inhibitors not only on the channel-opening probability but also on the opening and closing rates of the AChR channel. The transient kinetic measurements led to two predictions. (i) Ligands that bind to a regulatory site on the closed-channel conformation of the AChR with higher affinity than to the site on the open-channel form shift the equilibrium toward the closed-channel form, thereby inhibiting the receptor. (ii) Ligands that bind to a regulatory site with an affinity for the open conformation equal to or higher than their affinity for the closed conformations are expected not to inhibit the receptor and to displace inhibitors. The identification of such ligands in a combinatorial library of RNA ligands is reported. The implication of this approach to other protein-mediated reactions in which an inhibitor changes the equilibrium between active and inactive conformations is discussed.

Animals↗

Empirical Bayes approach to estimating the number of HIV-infected individuals in hidden and elusive populations.

In this paper we estimate the numbers of intravenous drug users (IVDUs) and commercial sex workers (CSWs) in Thailand infected with human immunodeficiency virus (HIV) who have not developed acquired immunodeficiency syndrome (AIDS) directly from the semi-annual HIV serosurveillance data of Thailand from June 1993 to June 1995. We propose a 'generalized removal model for open populations' for estimating HIV-infected population size within a hidden, elusive, and perhaps high-risk population group, for all sampling time when capture probabilities vary with time. We apply empirical Bayes methodology to the generalized removal model for open populations by using the Gibbs sampler, a Markov chain Monte Carlo method. No assumption on the size of the hidden population in question is needed to implement this procedure. The statistical method proposed here requires very little computing and only a minimum of two sets of serosurvey data to obtain an estimate, thereby providing a simple and viable option in epidemiological studies when either powerful computing facilities or abundant sampling data are lacking.

Bayes Theorem↗

O6-methylguanine formation, repair protein depletion and clinical outcome with a 4 hr schedule of temozolomide in the treatment of advanced melanoma: results of a phase II study.

O6-Methylguanine-DNA methyltransferase (MGMT) is a major determinant of resistance to temozolomide. Its levels are depleted in lymphocytes after drug administration, but there is partial recovery by 24 hr, the usual time of subsequent dosing. Administering subsequent doses of temozolomide at the MGMT nadir could enhance its effectiveness, by increasing the amount of O6-methylguanine (O6-meG) in DNA. We evaluated the efficacy of such a schedule of temozolomide and determined the kinetics of MGMT depletion and O6-meG formation in DNA following treatment. Thirty patients with advanced malignant melanoma were treated with temozolomide 1,000 mg/m2 equally split into 5 doses over a 16 hr period every 28 days. O6-meG formation was determined in peripheral blood mononuclear cell (PBMC) DNA and, in a subset of patients, in tumor tissue during the first treatment cycle. MGMT levels fell rapidly with dosing, reaching a nadir in PBMCs of 18.0 +/- 2.26% of initial levels. O6-meG levels increased during the treatment period, peaking at 11.1 +/- 1.25 micromol/mol dG in PBMCs and at 4.25 +/- 0.79 micromol/mol dG in tumor biopsies. The main toxicities were grade IV thrombocytopenia in 12 patients (42.8%) and grade IV neutropenia in 11 patients (39.2%), associated with fever in 8 cases. There were 7 responses (1 complete), for an overall response rate of 23.3%; median overall survival was 6.1 months. The compressed schedule has activity against melanoma, with greater MGMT depletion and O6-meG formation than previously reported for O6-alkylating agent regimens. Myelosuppression precludes its wider application, but MGMT in PBMCs predicted the dose intensity of temozolomide that patients could sustain, suggesting a means by which individuals suitable for this approach might be identified.

Adult↗

Indications of proximal thoracic curve fusion in thoracic adolescent idiopathic scoliosis: recognition and treatment of double thoracic curve pattern in adolescent idiopathic scoliosis treated with segmental instrumentation.

STUDY DESIGN: A retrospective study. OBJECTIVES: To determine the indications of fusing the proximal thoracic curve when treating idiopathic thoracic scoliosis with segmental instrumentation. SUMMARY OF BACKGROUND DATA: Failure to recognize a significant proximal thoracic curve often results in postoperative shoulder asymmetry due to relative overcorrection of the lower thoracic curve. With segmental instrumentation that enhances the correction of the instrumented curve, the double thoracic curve pattern that needs fusion of both the proximal and the distal thoracic curves should be redefined. METHODS: Forty patients with thoracic adolescent idiopathic scoliosis with a right lower thoracic curve of more than 40 degrees and a left proximal thoracic curve of more than 25 degrees treated by segmental pedicle screw instrumentation were analyzed after a minimum follow-up of 2 years. RESULTS: Of the 40 patients, 18 were treated by fusion of both the proximal and the distal curves, whereas 22 were treated by fusion of the distal curve only. The postoperative shoulder height difference (SHD, in millimeters) was 0.9 x preoperative SHD + 5.3 for the fusion of both curves and 0.6 x preoperative SHD + 12 for the distal curve fusion (linear regression), showing that proximal thoracic curve fusion improved the SHD when the left shoulder was level with or higher than the right. CONCLUSIONS: Idiopathic thoracic scoliosis with a proximal thoracic curve of more than 25 degrees and level or elevated left shoulder should be considered a double thoracic curve pattern and should be treated by fusing both the proximal and the distal curves when using segmental instrumentation.

Adolescent↗

The beneficial effect of ATP-MgCl(2) on hepatic ischemia/reperfusion-induced mitochondrial dysfunction.

The present study was undertaken to determine whether ATP-MgCl(2) administration in rats could protect hepatic mitochondrial function and improve energy metabolism during hepatic ischemia and subsequent reperfusion. Global hepatic ischemia was produced for 60 min followed by reperfusion. The rats then received 0.5 ml of saline or ATP-MgCl(2) intravenously. In saline-treated ischemic rats, serum alanine-aminotransferase levels peaked at 5 h. The aminotransferase level was significantly reduced in the ATP-MgCl(2) treatment group. The wet weight-to-dry weight ratio of the liver was significantly increased by ischemia/reperfusion. ATP-MgCl(2) treatment minimized the increase in this ratio. The ketone body ratio in blood, which reflects the mitochondrial free NAD(+)/NADH ratio, decreased after ischemia and at 1 h following reperfusion. This decrease was somewhat improved by ATP-MgCl(2) infusion. At 1 and 5 h after reperfusion, mitochondrial monoamine oxidase and glutamate dehydrogenase activities decreased. ATP-MgCl(2) infusion following ischemia restored the lost activities. Hepatic ATP levels in saline-treated rats were found to be 50% lower 5 h following reperfusion; however, treatment with ATP-MgCl(2) resulted in significantly higher ATP levels and energy charge. The accumulation of purine catabolites in ischemic tissues was reduced during reperfusion. ATP-MgCl(2) infusion resulted in accumulation of adenosine in reperfused liver. Mitochondrial lipid peroxidation was elevated in the saline-treated ischemic group, but this elevation was inhibited by ATP-MgCl(2) infusion. The present results lead us to conclude that the amelioration of liver function which occurs with ATP-MgCl(2) infusion following ischemia may be mediated through improvement in ischemia-induced mitochondrial energy metabolism.

Adenine Nucleotides↗

The biochemical and molecular characterization of recombinant Bacillus subtilis tripeptidase (PepT) as a zinc-dependent metalloenzyme.

Aminopeptidases catalyze the release of N-terminal amino acid residue from polypeptides and peptides, and most of them are known to be metalloenzymes. A tripeptidase gene (pepT) of Bacillus subtilis was expressed in Escherichia coli, and the resulting recombinant PepT was purified in an active form through sequential chromatographies. The addition of Zn2+ or Co2+ increased the enzymatic activity by approximately two fold. The points at which Zn2+ and Co2+ stimulated a half-maximum activity of the PepT were 650 nM and 1,700 nM, respectively. The measurement of the metal content showed that this enzyme contained 0.26 atom of Zn2+ per molecule with essentially the absence of Co2+ and others, and 0.53 atom of Zn2+ with 1.5-fold increase of activity when reconstituted with Zn2+. Consistent with this result, this enzyme is much readily refolded in the presence of Zn2+ than Co2+. To further delineate the structure and function relations, we made serial deletion mutants and analyzed their enzymatic activities. Of eight deletion mutants, only a mutant lacking the N-terminal 66 amino acid residues retained enzymatic activity. The mutant enzyme, however, required a concentration of Zn2+ ion at least ten-fold higher to reach maximum activity without significantly affecting kinetic parameters such as Km and Vmax compared to the full length PepT. Taken together, these data suggest that the B. subtilis PepT is likely to be a Zn2+-dependent metalloenzyme and that the N-terminal region of the PepT stabilizes Zn2+-binding.

Amino Acid Sequence↗

Neutralization epitopes on the antigenic domain II of the Orientia tsutsugamushi 56-kDa protein revealed by monoclonal antibodies.

Monoclonal antibodies (MoAbs) reactive with the authentic Orientia tsutsugamushi 56-kDa protein were generated. MoAb FS10 and FS15 showed in vitro, as well as, in vivo neutralizing activity upon O. tsutsugamushi infection. Deletion mutants of the gene for 56-kDa protein of O. tsutsugamushi Boryong were expressed to map the binding region. FS10 and FS15 are bound to amino acids (aa) located in an antigenic domain II, at residues 140-160 and 187-214, respectively. Computer modeling indicated that aa 146-153 were important for antigenicity against FS10. A sequence for aa 142-150 was highly homologous between oriential strains. These results suggest that the antigenic determinant for neutralizing MoAbs is an epitope within aa 140-160. Furthermore, this region may be important for the adhesion/invasion or intracellular survival of O. tsutsugamushi within host cells.

Amino Acid Sequence↗

Evidence that ginsenosides prevent the development of opioid tolerance at the central nervous system.

The analgesic effect of ginsenosides or morphine was first determined following intrathecal (i.t.) administration in rat tail-flick test. The effect of chronic i.t. co-administration of ginsenosides with morphine on the development of opioid tolerance were also examined using rat tail-flick test. Administration of ginsenosides (i.t.) produced a weak antinociception in a dose-dependent manner. Administration of morphine (i.t.) also produced antinociception in a dose-dependent manner. The ED50 was 1.20 microg (1.14-1.29 microg). However, acute i.t. co-administration of ginsenosides with morphine was not additive in antinociception. Repeated i.t. co-administration of 200 microg ginsenosides with 10 microg morphine inhibited the development of tolerance induced by 10 microg morphine in rat tail-flick test, although i.t. co-administration of 50 or 100 microg ginsenosides with morphine was without effect. In conclusion, these results indicate that i.t. administered ginsenosides produce an antinociception in rat tail-flick test and also prevent opioid tolerance caused by chronic treatment with morphine at the spinal sites.

Analgesics, Opioid↗

Interaction of hCLIM1, an enigma family protein, with alpha-actinin 2.

Enigma proteins are proteins that possess a PDZ domain at the amino terminal and one to three LIM domains at the carboxyl terminal. They are cytoplasmic proteins that are involved with the cytoskeleton and signal transduction pathway. By virtue of the two protein interacting domains, they are capable of protein-protein interactions. Here we report a study on a human Enigma protein hCLIM1, in particular. Our study describes the interaction of the human 36 kDa carboxyl terminal LIM domain protein (hCLIM1), the human homologue of CLP36 in rat, with alpha-actinin 2, the skeletal muscle isoform of alpha-actinin. hCLIM1 protein was shown to interact with alpha-actinin 2 by yeast two-hybrid screening and immunochemical analyses. Yeast two-hybrid analyses also demonstrated that the LIM domain of hCLIM1 binds to the EF-hand region of alpha-actinin 2, defining a new mode of LIM domain interactions. Immunofluorescent study demonstrates that hCLIM1 colocalizes with alpha-actinin at the Z-disks in human myocardium. Taken together, our experimental results suggest that hCLIM1is a novel cytoskeletal protein and may act as an adapter that brings other proteins to the cytoskeleton.

Actinin↗

Role of Kupffer cells in cold/warm ischemia-reperfusion injury of rat liver.

The mechanisms of liver injury from cold storage and reperfusion are not completely understood. The aim of the present study was to investigate whether the inactivation of Kupffer cells (KCs) by gadolinium chloride (GdCl3) modulates ischemia-reperfusion injury in the rat liver. Hepatic function was assessed using an isolated perfused rat liver model. In livers subjected to cold storage at 4 degees C in University of Wisconsin solution for 24 hrs and to 20 min rewarm-ing ischemia, oxygen uptake was markedly decreased, Kupffer cell phagocytosis was stimulated, releases of purine nucleoside phosphorylase and lactate dehydrogenase were increased as compared with control livers. Pretreatment of rats with GdCl3, a selective KC toxicant, suppressed Kupffer cell activity, and reduced the grade of hepatic injury induced by ischemia-reperfusion. While the initial mixed function oxidation of 7-ethoxycoumarin was not different from that found in the control livers, the subsequent conjugation of its meta-bolite to sulfate and glucuronide esters was suppressed by ischemia-reperfusion. GdCl3 restored sulfation and glucuronidation capacities to the level of the control liver. Our findings suggest that Kupffer cells could play an important role in cold/warm ischemia-reperfusion hepatic injury.

Animals↗

Cytotoxic triterpenes from Crataegus pinnatifida.

Bioassay-guided fractionation of Crataegus pinnatifida (Rosaceae) gave two cytotoxic ursane-type triterpenes which were identified as uvaol (1) and ursolic acid (2) by physicochemical and spectroscopic methods. 3-Oxo-ursolic acid (3) was synthesized from ursolic acid (2) by Jones method. The cytotoxic activities of these compounds were tested against murine L1210 and human cancer cell lines (A549, SK-OV-3, SK-MEL-2, XF498, and HCT15) in vitro. Compounds 1 and 2 showed moderate cytotoxicities against L1210, whereas they showed weak activities against human cancer cell lines. However, compound 3 exhibited potent cytotoxic activities both in murine and in human cancer cell lines.

Animals↗

Effect of S-adenosylmethionine on hepatic injury from sequential cold and warm ischemia.

We investigated whether S-adenosylmethionine (SAM) treatment improved ischemic injury using perfused rat liver after sequential periods of 24 h cold and 20 min re-warming ischemia. SAM (100 micromol/L) was added to University of Wisconsin (UW) solution and Ringers lactate solution. After cold and sequential warm ischemia, releases of lactate dehydrogenase (LDH) and purine nucleoside phosphorylase (PNP) markedly increased during reperfusion. The increase in PNP was significantly reduced by SAM treatment. While the concentration of reduced glutathione (GSH) in ischemic livers significantly decreased, the concentration of glutathione disulfide (GSSG) increased. This decrease in GSH and increase in GSSG were suppressed by SAM treatment. Lipid peroxidation was elevated in cold and warm ischemic and reperfused livers, but this elevation was also prevented by SAM treatment. Hepatic ATP levels were decreased in the ischemic and reperfused livers to 42% of the control levels. However, treatment with SAM resulted in significantly higher ATP levels and preserved the concentration of AMP in ischemic livers. Our findings suggest that SAM prevents oxidative stress and lipid peroxidation and helps preserve hepatic energy metabolism.

Adenosine Triphosphate↗

Ultrasonography of the shoulder.

Musculoskeletal ultrasound (MSUS) is an important modality in evaluating shoulder disease. Following a baseline shoulder conventional radiographic examination, MSUS can be used to screen the painful shoulder. It is accurate in diagnosing full- and partial-thickness tears of the rotator cuff. Both types of tears can be further characterized by size, location, and extension. Postoperatively, the rotator cuff can also be evaluated for recurrent full-thickness tears. MSUS is the only modality that can visualize and characterize synovial disease, without radiographic contrast, and when necessary, US-guided aspiration and biopsy can be performed. Real-time scanning shows the actual motion of the shoulder and its parts. Multiple attempts can be made to achieve optimal images for accurate documentation. Accessibility to MSUS facilitates the rapid turnaround of patients. US imagers and bone radiologists would do well to use MSUS to help their referring physicians establish a quick and accurate diagnosis of shoulder disorders. This article presents a comprehensive, pictorial review of the technical aspects of shoulder sonography as well as major types of pathology that can be diagnosed with US.

Arthrography↗

Patterns of relapse and subsequent management following high-dose chemotherapy with autologous haematopoietic support in relapsed or refractory Hodgkin's lymphoma: a two centre study.

BACKGROUND: High-dose chemotherapy has an established role in recurrent or refractory Hodgkin's lymphoma (HL) although a significant proportion of patients subsequently relapse. This manuscript describes the clinical characteristics of such patients and documents their further management at two major UK cancer centres. PATIENTS AND METHODS: Between 1987 and 1996 one hundred patients with recurrent or refractory HL received high-dose chemotherapy (HDCT) with autologous haematopoietic rescue. All had recurred within 12 months of initial therapy or had two or more recurrences. RESULTS: With a median follow-up of 2 years, 56 patients are currently progression-free. There were six treatment-related deaths. One patient died of pneumonia in remission. Thirty-seven patients have relapsed, intrapulmonary disease being seen for the first time in 53% and recurrence at previous sites of disease in 81%. Following recurrence, therapy was determined by circumstances: either one agent at a time was used (single sequential approach) or multiagent chemotherapy was chosen. There was a survival advantage for those who achieved a symptomatic response (13 vs. 4 months median, P = 0.0001). A trend towards longer survival was seen for those whose disease recurred beyond six months following high-dose chemotherapy and in those who received combination chemotherapy. CONCLUSIONS: These results confirm that HDCT with autologous haematopoietic support is inadequate for about half the patients who receive it for high-risk HL. Relapse in the site of prior disease is the most likely pattern with intrapulmonary disease for the first time occurring frequently. It is possible to administer further chemotherapy after failure of HDCT, and both objective as well as subjective benefit can be achieved. A few patients appear to get long-term benefit from further treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Choroidal Langerhans' cell histiocytosis.

PURPOSE: To report a patient with choroidal Langerhans' cell histiocytosis. METHODS: A solitary tumor was found in the left eye of a 49-year-old male who had no definite history of systemic disorders, but had observed visual disturbances for a period of 1 month. Ultrasonography, fluorescein angiography, and indocyanine green angiography were performed and the eyeball was enucleated. We prepared the specimen for microscopic examinations. RESULTS: Fluorescein angiographic findings of the lesion were mottled hyperfluorescence in the arteriovenous phase and strong hyperfluorescence in the late phase. Hypofluorescence in both early and late phases showed on indocyanine green angiogram. The lesion of choroid was widely infiltrated by histiocytes, though no extraocular invasion was found. Immunohistochemical studies including S-100 and CD 68 staining revealed characteristic features of Langerhans' cell histiocytosis. Electron microscopic examination of the histiocytes showed histiocytosis X body (Birbeck granule) in the cytoplasm and indented nucleus. CONCLUSION: We consider that this is a case of choroidal Langerhans' cell histiocytosis with no evidence of systemic lesions.

Antigens, CD↗

Localization of a major allergen, Der p 2, in the gut and faecal pellets of Dermatophagoides pteronyssinus.

BACKGROUND: The house dust mite Dermatophagoides ptronyssinus is one of the most significant indoor sensitizing agents of allergy. Allergen localization may indicate the importance of secreted materials, faeces, and nonexcreted mite body components as allergen sources. OBJECTIVE: This study attempted to localize the sites and concentrations of Der p 2 in the cryostat sections of D. pteronyssinus using antirecombinant Der p 2 monoclonal antibody. METHODS: Male and female mites and mite faeces collected separately from both sexes were used. Live mites were embedded and serial cryostat sections for light microscopy were performed. Anti-recombinant Der p 2 monoclonal antibody previously produced by the authors was used. For immunoprobing, mite cryostat sections were incubated in the following antibody-containing solutions: monoclonal antibody against Der p 2 was initially applied to the sections and fluorescent isothiocyanate conjugated antimouse immunoglobulin G was reacted as the secondary antibody. The faecal pellets were treated the same as described above. RESULTS: Immunofluorescent probing of cryostat sections with the monoclonal antibody showed labelling of the gut lining, gut contents and defecated faecal pellets. No other internal organs were identified as positively labelled. CONCLUSION: This study suggested that a major allergen, Der p 2, found in the house dust mite D. pteronyssinus is derived from the digestive tract and concentrated in the faeces.

Allergens↗