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Biomedical subjects

S M Lee

Publications and source records attributed to S M Lee.

At least 19 recordsLinked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

A randomized phase III study comparing dacarbazine, BCNU, cisplatin and tamoxifen with dacarbazine and interferon in advanced melanoma.

The purpose of this study was to compare the response rate, overall and 1-year survival in patients with advanced melanoma treated with a standard therapy, dacarbazine and interferon-alpha (DTIC/IFN), or combination chemotherapy, consisting of dacarbazine, BCNU, cisplatin and tamoxifen (DBCT). Treatment toxicity and time spent in hospital were secondary end points. One hundred and five patients (of whom 100 were eligible) were randomized to receive either DTIC/IFN or DBCT. The trial was designed to detect a 25% absolute difference in response rate or in 1-year survival with 80% power. There was no significant difference in response rate: this was 17.3% with DTIC/IFN and 26.4% with DBCT. Median overall survival was similar at 199 and 202 days respectively. One-year survival rate favoured standard treatment (30.6 vs 22.6%), but did not differ significantly between arms. DBCT was associated with significantly greater haematological toxicity, and a greater need for time spent in hospital (5.75 days/treatment cycle vs 2.29 with dacarbazine and interferon). DBCT combination therapy cannot be recommended as standard treatment for advanced melanoma. Dacarbazine remains the standard chemotherapy for this condition.

Adult↗
PubMed2000

A comparative pharmacodynamic study of IY-81149 versus omeprazole in patients with gastroesophageal reflux disease.

OBJECTIVE: To evaluate and compare the pharmacodynamic effects of IY-81149 and omeprazole on gastric pH in patients with gastroesophageal reflux disease. METHODS: Sixty male and female volunteers with gastroesophageal reflux disease were enrolled in a double-blind, two-way, crossover, dose-ranging study. Subjects were randomized into three groups, with each group comparing the effect of one of three doses of IY-81149 (5, 10, or 20 mg) with 20 mg omeprazole. IY-81149 and omeprazole were administered once daily for 5 days. Continuous 24-hour pH measurements were performed before the first dose (baseline) and after the fifth dose in both periods. Gastric acid suppression was evaluated on the basis of the following parameters: AUC(0-24), median pH in a 24-hour interval (pHmedian), and the percent time in a 24-hour interval in which the gastric pH was greater than 4 (tpH > 4). The truncated AUC parameters AUC(0-8), AUC(8-16), and AUC(16-24) were also calculated. The effects of IY-81149 and omeprazole on gastric pH were compared by use of analyses of covariance. The dose-response relationship for IY-81149 was also evaluated. RESULTS: There were no statistically significant differences between 5 mg IY-81149 and 20 mg omeprazole in terms of AUC(0-24), pHmedian, tpH, 4, AUC(0-8), and AUC(8-16). IY-81149, at 10 mg, produced a significantly greater gastric acid suppression than omeprazole on the basis of the values of AUC(0-24), pHmedian, tpH > 4, AUC(8-16), and AUC(16-24). Administration of 20 mg IY-81149 produced a significantly greater gastric acid suppression on the basis of all parameters. All doses of IY-81149 were more effective than omeprazole during 16 to 24 hours after the dose was administered. CONCLUSIONS: Administration of 10 and 20 mg IY-81149 produced a statistically significantly greater and prolonged suppression of gastric pH than 20 mg omeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Human intravenous immunoglobulin preparation and virus inactivation by pasteurization and solvent detergent treatment.

Human intravenous immunoglobulin (IVIG) solutions were prepared by two different methods and compared to each other. The crude immunoglobulin fraction obtained from Cohn-Oncley fractionation of plasma was further purified and subjected to virus inactivation, either by polyethylene glycol precipitation and pasteurization at 60 degrees C for 10 hours, or by ion exchange chromatography and solvent/detergent treatment. The final preparations, formulated in 5% immunoglobulin solutions were characterized by in vitro analyses of biochemical and biological properties and compared with the samples of other manufacturer's IVIG solution products. The critical properties evaluated in this study were purity, molecular intactness, and the biological functions such as Fc function and anticomplementary activity. Virus inactivation and removal by processing steps and by deliberate virucidal steps, as described above, were tested on various human pathogenic viruses, such as human immunodeficiency and experimental model viruses. The tested viruses were successfully inactivated and removed. We conclude that the intravenous immunoglobulins prepared by two different methods, as described above, provide an equivalent viral safety and quality.

Antibodies↗
PubMed2000

Ethanol reduces metabolic uncoupling following experimental head injury.

Previous investigations have shown that ethanol is neuroprotective following experimental traumatic brain injury (TBI). This study sought to determine if the neuroprotective effects of ethanol in a controlled cortical impact (CCI) injury model are related to its effects on cerebral glucose metabolism and blood flow. Adult rats were given ethanol (1.0 g/kg) or saline by intraperitoneal injection followed 40 min later by injury. Regional cerebral blood flow (CBF) and cerebral metabolic rates of glucose (CMRglc) were determined immediately, and at 3, 6, 12, 24, and 72 h postinjury using quantitative autoradiography. Immediately after injury, CMRglc in the contusion core and penumbra was reduced in the ethanol group compared to the saline group: (core CMRglc: 52.2 +/- 16.0 versus 94.2 +/- 14.1 micromol/100 g/min, respectively,p < 0.001; penumbral CMRglc: 58.2 +/- 12.8 versus 82.8 +/-19.7 micromol/100 g/min, respectively; p < 0.05) However, at 24 and 72 h postinjury, penumbral CMRglc in the ethanol group was increased compared to the saline group (p < 0.05 and p < 0.001, respectively). Regarding CBF, contusion core values in the ethanol group were elevated compared to the saline group immediately postinjury, (70.4 +/- 17.1 versus 31.5 +/- 27.8 mL/100 g/min, respectively (p < .05), and at 6, 12, and 24 h postinjury (p < 0.05). Penumbral CBF was also higher at 6 and 72 h in the ethanol group compared to the saline group (p < 0.05). These results indicate that low-dose ethanol is associated with a marked attenuation of immediate postinjury hyperglycolysis and with more normal glucose metabolism in the injury penumbra over the ensuing 3 days. Simultaneously, the reduction in CBF typically seen within the contusion core and penumbra after CCI is less severe when ethanol is present. The net effect of these changes is a decreased degree of uncoupling between glucose metabolism and CBF that otherwise occurs in the absence of ethanol. These changes may likely explain the neuroprotective effect of ethanol.

Animals↗
PubMed2000

Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury.

Utilizing [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), we studied the correlation between CMRglc and the level of consciousness within the first month following human traumatic brain injury. Forty-three FDG-PET scans obtained on 42 mild to severely head-injured patients were quantitatively analyzed for the determination of regional cerebral metabolic rate of glucose (CMRglc). Reduction of cerebral glucose utilization, defined as a CMRglc of < or =4.9 mg/100 g/min, was present regionally in 88% of the studies. The prevalence of global cortical CMRglc reduction was higher in severely head-injured patients (86% versus 67% mild-moderate), although the absolute magnitude was similar across the injury severity spectrum (mean CMRglc 3.9 +/- 0.6 mg/100 g/min). The level of consciousness, as measured by the Glasgow Coma Scale, correlated poorly with the global cortical CMRglc value (r = 0.08; p = 0.63). With regards to severity of head injury, this correlation was worst for the severely injured (r = -0.11; p = 0.58) and better for the mildly injured patients (r = 0.50; p = 0.07). In most cases, intraparenchymal hemorrhagic lesions were associated with either focal CMRglc reduction or elevation. It is concluded that the etiologies of CMRglc reduction are likely multifactorial given the complex nature of traumatic brain injury and that the reduction of CMRglc represents a fundamental pathobiologic state following head injury that is not tightly coupled to level of consciousness.

Adult↗
PubMed2000

Inhibition of neocortical plasticity during development by a moderate concussive brain injury.

To determine if a moderate traumatic brain injury (TBI) sustained early in life alters the capacity for developmental plasticity, 17-20-day-old rat pups received a lateral fluid percussion and then reared in an enriched environment for 17 days. Compared to sham-injured controls, this moderate TBI prevented the increase in cortical thickness (1.48 vs. 1.68 mm, p < 0.01) as well as the corresponding enhancement in cognitive performance in the Morris Water Maze (39 vs. 25 trials to criterion, p < 0.05). These injured animals exhibited no significant neuronal degeneration and no evidence of neurologic or motor deficits. These findings strongly support the conclusion that a diffuse brain injury is capable of inhibiting both anatomical and cognitive manifestations of experience-dependent developmental plasticity.

Animals↗