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Biomedical subjects

S Y Oh

Publications and source records attributed to S Y Oh.

At least 19 recordsLinked to original sources
PubMed2001

Ether fraction of methanol extracts of Gastrodia elata, a traditional medicinal herb, protects against kainic acid-induced neuronal damage in the mouse hippocampus.

Gastrodia elata (GE) has been used traditionally for the treatment of convulsive diseases such as epilepsy in oriental countries including South Korea and still occupies an important place in traditional medicine in Asia. We studied the anticonvulsive effect and protective effect of the ether fraction of methanol extracts (EFME) of GE against hippocampal neuronal damage after kainic acid administration in mice. Mice were treated with the EFME of GE (200 or 500 mg/kg per day, p.o.) for 14 days before kainic acid injection (45 mg/kg, i.p.). The EFME of GE (at the dose of 500 mg/kg) delayed the onset time of neurobehavioral change (P<0.01) and reduced the severity of convulsions (P<0.05) and hippocampal neuronal damage in the CA1 (P<0.01) and CA3 (P<0.05) regions. Our results show that The EFME of GE has anticonvulsive effect and putative neuroprotective effect against excitotoxicity induced by kainic acid.

Animals↗
PubMed2001

Activation of heat shock factor 1 by pyrrolidine dithiocarbamate is mediated by its activities as pro-oxidant and thiol modulator.

Pyrrolidine dithiocarbamate (PDTC) is known to inhibit NF-kappa B, which plays a critical role(s) as an immediate early mediator of immune and inflammatory responses. Here we show that PDTC induces heat shock factor 1 (HSF1) activation and heat shock protein expression, while other antioxidants such as butylated hydroxytoluene (BHT), n-propylgallate (PG), ascorbic acid (AA), and N-acetyl-L-cysteine (NAC) do not. Since PDTC exerts other functions than antioxidant, e.g., a pro-oxidant, metal chelator, and thiol group modulator, we examined which of these activities is responsible for the PDTC-induced HSF1 activation. PDTC-induced HSF1 activation was not prevented by metal chelators, EDTAs, indicating that the metal chelating effect of PDTC is not linked to the HSF1 activation. PDTC increased intracellular GSSG level. In addition, PDTC-induced activation of HSF1 was significantly inhibited by NAC and a thiol-reducing agent dithiothreitol (DTT), while it was partially prevented by other antioxidants, AA, BHT, and PG. These results suggest that the activation of HSF1 by PDTC may be due to its activities as pro-oxidant and thiol group modulator rather than anti-oxidant.

Acetylcysteine↗
PubMed2001

IgE binding components in Tetranychus urticae and Panonychus ulmi-derived crude extracts and their cross-reactivity with domestic mites.

BACKGROUND: Recent investigation has revealed that spider mites such as Tetranychus urticae and Panonychus ulmi are important allergens in the development of occupational asthma among apple farmers. OBJECTIVE: To evaluate IgE binding components in T. urticae and P. ulmi-derived crude extracts and their cross-reactivity with Panonychus citri, Tyrophagus putrescentiae and Dermatophagoides pteronyssinus in apple cultivating farmers. METHODS: Thirty-one apple farmers with positive skin responses to T. urticae or P. ulmi were randomly recruited, and specific IgE levels in their sera were measured using ELISA. Cross-reactivity was evaluated by ELISA inhibition. IgE binding components were evaluated by IgE immunoblotting. RESULTS: A total of 11 IgE binding components in T. urticae and 10 in P. ulmi were found. Among them, the 17 kDa, 27 kDa, 33 kDa, 37 kDa, 41 kDa, 56 kDa, and 75 kDa allergens in T. urticae, and the 33 kDa, 41 kDa, and 51 kDa allergens in P. ulmi were identified as dominant allergens. T. urticae-specific IgE binding was completely inhibited by 100 microg/mL of T. urticae (99.7%), but only partially inhibited by P. citri (83.0%), P. ulmi (71.6%), T. putrescentiae (69.7%), and D. pternonyssinus (60.1%). P. ulmi-specific IgE binding was completely inhibited by additions of P. citri (92.3%) and P. ulmi (91.2%), but only partially inhibited by the addition of T. urticae (61.5%), T. putrescentiae (57.7%), and D. pteronyssinus (54.4%). CONCLUSION: There were seven dominant allergens found in T. urticae and three in P. ulmi. T. urticae- and P. ulmi-specific IgE bindings were partially inhibited by crude extracts derived from D. pteronyssinus and T. putrescentiae.

Adult↗
PubMed2001

The relationship between oligohydramnios and the onset of preterm labor in preterm premature rupture of membranes.

OBJECTIVE: The objective of this study was to determine whether a reduced amniotic fluid volume was associated with the onset of preterm parturition in patients with preterm premature rupture of membranes. STUDY DESIGN: An amniotic fluid index was determined before transabdominal amniocentesis in 129 patients with preterm premature rupture of membranes (gestational age < or = 35 weeks). Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Survival techniques were used for analysis. RESULTS: Amniotic fluid index was < or = 5 cm in 29% of patients (38/129). Patients with an amniotic fluid index of < or = 5 cm had a significantly higher rate of positive amniotic fluid culture than those with an amniotic fluid index of >5 cm (42% [16/38] vs 18% [16/91]; P<.01). Spontaneous preterm delivery within 24 hours and 48 hours was more frequent among patients with an amniotic fluid index of < or = 5 cm than those with an amniotic fluid index of >5 cm (for 24 hours, 29% vs 12%; for 48 hours, 42% vs 21%; P<.05 for each). The amniocentesis-to-delivery interval was significantly shorter in patients with an amniotic fluid index of < or = 5 cm than in patients with an amniotic fluid index of >5 cm (median, 38 hours; range, 0.2-1310 hours; vs median, 100 hours; range 0.1-2917 hours; P<.01). Moreover, Cox proportional hazards model analysis indicated that an amniotic fluid index of < or = 5 cm was a significant predictor of the duration of the pregnancy after adjustment for gestational age and the results of amniotic fluid culture (odds ratio, 2.4; 95% confidence interval, 1.4-3.9; P<.001). CONCLUSION: Patients with preterm premature rupture of membranes and an amniotic fluid index of < or = 5 cm are at increased risk for a shorter interval to delivery.

Adult↗
PubMed2001

An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery.

OBJECTIVE: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid matrix metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. STUDY DESIGN: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. RESULTS: The median amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (matrix metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, <0.3-45.2 ng/mL], P <.01; interleukin-6: median, 0.32 ng/mL [range, 0.04-2.52 ng/mL] vs median, 0.18 ng/mL [range, 0.01-1.81 ng/mL], P <.01; angiogenin: median, 11.1 ng/mL [range, 4.5-30.7 ng/mL] vs median, 6.7 ng/mL [range, 1.3-21.9 ng/mL], P <.001). Amniotic fluid matrix metalloproteinase-8 concentrations higher than 23 ng/mL had the highest specificity and odds ratio (sensitivity, 42% [8/19]; specificity, 99% [94/95]; OR, 68.4 [95% CI, 7.8-599.1]) in the identification of the patients with preterm delivery after genetic amniocentesis. CONCLUSIONS: Elevated mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery (<32 weeks). An elevated matrix metalloproteinase-8 level of >23 ng/mL is a powerful predictor of spontaneous preterm delivery (<32 weeks) with an odds ratio of 68.4. Amniotic fluid studies can be used to improve the risk assessment for preterm delivery in women who undergo mid-trimester amniocentesis for genetic indications.

Adult↗
PubMed2001

The relationship between amniotic fluid matrix metalloproteinase-8 and funisitis.

OBJECTIVE: The fetal inflammatory response syndrome is a multisystem disorder associated with impending preterm delivery and adverse neonatal outcome. Inflammation of the umbilical cord--funisitis--is the histologic counterpart of fetal inflammatory response syndrome and has been associated with an increased risk for the development of cerebral palsy. Neutrophils found in the amniotic cavity are of fetal origin. Therefore, neutrophil secretory products may be an index of the fetal inflammatory response syndrome. To test this hypothesis, we examined the relationship between levels of amniotic fluid matrix metalloproteinase-8 and funisitis. STUDY DESIGN: The relationship between the presence of funisitis and concentrations of amniotic fluid matrix metalloproteinase-8 was examined in 255 consecutive patients who delivered preterm singleton neonates (gestational age, <36 weeks) within 72 hours of amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. Matrix metalloproteinase-8 was measured by use of a specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: Funisitis was present in 23% (59/255) of cases. Patients with funisitis had a significantly higher median concentration of amniotic fluid matrix metalloproteinase-8 than those without funisitis (median, 433.7 ng/mL [range, 1.5-3836.8 ng/mL] vs median, 1.9 ng/mL [range, <0.3-4202.7 ng/mL]; P <.001). The diagnostic indices of matrix metalloproteinase-8 (cutoff, 23 ng/mL) in the identification of funisitis were: sensitivity of 90% (53/59), specificity of 78% (153/196), positive predictive value of 55% (53/96), and negative predictive value of 96% (153/159). CONCLUSIONS: There is a strong association between increased levels of amniotic fluid matrix metalloproteinase-8 and funisitis. We propose that determination of amniotic fluid matrix metalloproteinase-8 concentrations may assist the assessment of the fetal inflammatory status, thereby eliminating the need for fetal blood sampling.

Adult↗
PubMed2001

The frequency and clinical significance of intra-amniotic inflammation in patients with a positive cervical fetal fibronectin.

OBJECTIVE: A positive fetal fibronectin result in cervicovaginal fluid is a powerful predictor of preterm delivery and is considered a marker for upper genital tract infection (ie, intrauterine infection). Treatment with antimicrobial agents is being considered in patients with a positive fetal fibronectin test of cervico/vaginal fluid. This study was undertaken to determine the frequency and clinical significance of intra-amniotic infection/inflammation in patients with a positive fetal fibronectin. STUDY DESIGN: A total of 1709 pregnant women (gestational age, 23-31 weeks) were screened for cervical fetal fibronectin. Patients with a positive fibronectin were offered amniocentesis for the diagnosis of intra-amniotic infection and treatment with antibiotics. Amniocentesis was performed in 58 patients with a positive fibronectin test (>50 ng/mL). Amniotic fluid was cultured for aerobic/anaerobic bacteria and mycoplasmas. Polymerase chain reaction assay for Ureaplasma urealyticum was performed. Interleukin-6 concentrations were measured by a specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: None of the patients with a positive fibronectin had a positive amniotic fluid culture. U urealyticum was detected in 1 case (1.8%) with the polymerase chain reaction assay. Amniotic fluid IL-6 was elevated (>2.5 ng/mL) in 5.3% of patients (3/57 patients); all of these patients delivered preterm neonates. There was no relationship between amniotic fluid IL-6 and cervical fibronectin concentration (r = 0.14;P: >.1). Patients who delivered preterm (<34 weeks) had higher median amniotic fluid IL-6 and cervical fetal fibronectin concentrations than those patients who delivered after 34 weeks (IL-6: median, 2.1 ng/mL [range, 0.1-25.3 ng/mL] vs median, 0.3 ng/mL [0.03-2.4 ng/mL]; P <.05; fibronectin: median, 509 ng/mL [260->1000 ng/mL] vs median, 155 ng/mL [50-889 ng/mL]; P <.01). CONCLUSION: Intra-amniotic infection was detected in 1.8% of cases with a positive fibronectin in the cervical fluid; intra-amniotic inflammation was present in 5.3% of cases. All patients with a positive fetal fibronectin and intra-amniotic inflammation delivered preterm neonates.

Adult↗
PubMed2001

A randomized comparison of prism adaptation and augmented surgery in the surgical management of esotropia associated with hypermetropia: one-year surgical outcomes.

OBJECTIVE: To compare motor and sensory 1-year surgical outcomes in patients with hypermetropic esotropia, managed with either augmented surgery based on the average of the near deviation with and without correction or preoperative prism adaptation. METHODS: Forty-three patients with hypermetropic esotropia without distance-near disparity entered a randomized prospective evaluation of augmented surgery (group A, 27 patients) versus prism adaptation (group P, 16 patients). The formula for augmenting the amount of the rectus muscle recession was based on the average of the near deviation with and without correction in group A and the prism-adapted angle of deviation in group P. During prism adaptation, 9 of 16 patients in group P responded to prism. Motor and sensory outcomes of the Worth 4-dot test at 6 and 0.33 m and the Titmus stereotest were evaluated 1, 3, 6, and 12 months after surgery. RESULTS: Postoperative deviations of 8 PD or less at distance were achieved in 24 of 27 patients (89%) of group A and in 7 of the remaining 8 patients (88%) of prism responders and in all 7 prism nonresponders (100%) in group P. No significant difference existed between groups A and P, as well as between the prism responders and prism nonresponders in group P in terms of near and distance deviation 1 year after surgery. The sensory outcomes improved over time in group A and prism responders. CONCLUSION: There were no significant differences in the surgical outcomes between each group. However, the small sample size may limit the power to detect any statistically significant differences.

Adaptation, Ocular↗
PubMed2001

Quantitative analysis of rectus extraocular muscle layers in monkey and humans.

PURPOSE: Rectus extraocular muscles (EOMs) consist of orbital (OL) and global (GL) layers. This study enumerated the fibers in both layers along the length of each EOM. METHODS: Four human (ages 17 months-93 years) and three monkey (ages 5-7 years) orbits were serially sectioned in the coronal plane and stained with Masson's trichrome. All fibers of the rectus EOMs were counted using light microscopy at midorbit in all specimens and regular intervals throughout the orbits for one human and one monkey. RESULTS: In the GL, human EOMs in midorbit contained 8000 to 16,400 fibers, and monkey EOMs contained 3600 to 6600 fibers, varying little among the four rectus EOMs. In humans and monkeys, the number of OL fibers in midorbit varied widely according to specific EOM, being most numerous for the medial rectus (human: 7400-14,600; monkey: 3700-7000). The GL existed over the entire extent of each EOM from origin in the orbital apex into continuity with the tendon inserting on the globe. The OL was absent in the most anterior portion of each EOM, because OL fibers inserted on the respective EOM pulley. CONCLUSIONS: Primate EOMs contain substantial numbers of OL fibers. Numerical similarity of GL fibers is consistent with similar mechanical loading on each of the four rectus EOMs, as required to rotate the globe. Numerical dissimilarity of OL fibers correlates with varying mechanical loading because of varying elasticities of connective tissues onto which these fibers insert.

Adolescent↗
PubMed2001

Structure-function correlation of laminar vascularity in human rectus extraocular muscles.

PURPOSE: Orbital and global layers of rectus extraocular muscles (EOMs) are believed to serve different functions. This study sought anatomic and functional evidence of differing blood flow in the two layers of rectus EOMs. METHODS: Four human orbits ranging in age from 17 months to 93 years were serially sectioned and stained for muscle fibers with Masson's trichrome and for vascular smooth muscle with monoclonal antibody to smooth muscle alpha-actin. Digitally assisted microscopy was used to obtain measurements of luminal cross sections and counts of muscular blood vessels, as well as measurements of muscle fiber number and cross-sectional areas of the two layers. Findings were correlated with first-pass gadodiamide contrast magnetic resonance imaging (MRI) in two living humans to demonstrate relative perfusion of EOMs. RESULTS: In all rectus EOMs, the orbital layer had significantly more vessels per unit area, more vessels per fiber, and more total vascular luminal area, than the global layer (P: < 0.05). Vascularity of EOMs was greatest in the youngest specimen. First-pass contrast MRI was consistent with perfusion of the orbital layer earlier than the global layer of living human rectus EOMs. CONCLUSIONS: Orbital layers of human rectus EOMs have significantly more muscular vessels than the global layers and stain earlier after intravenous bolus injection of paramagnetic MRI contrast. These findings suggest higher and even more rapid blood flow in the orbital layers that may correlate with greater metabolic activity. Greater blood flow is consistent with more sustained mechanical loading of the orbital than the global layer.

Adult↗
PubMed2001

HLA-DRB1*07 may have a susceptibility and DRB1*04 a protective effect upon the development of a sensitization to house dust mite Dermatophagoides pteronyssinus.

BACKGROUND: IgE responses to house dust mite-derived allergens seem to be the most important in the development of atopic asthma and rhinitis, but it has been difficult to demonstrate genetic control of the IgE response to the allergens. OBJECTIVE: This study was undertaken to investigate the association between sensitization to house dust mite, D. pteronyssinus (DP), and genotypes of HLA-DRB1 alleles. METHODS: DNAs were extracted from two groups of unrelated Koreans: (1) 178 with sensitization to DP; and (2) 99 age-matched non-atopic controls. Genotypes of the HLA-DRB1 alleles were determined using polymerase chain reaction (PCR)-based methods. RESULTS: The frequency of HLA-DRB1*07 was significantly increased in the DP-sensitive subjects compared with the controls (15.7% vs 4.0%, P = 0.009). Conversely, the frequencies of HLA-DRB1*04 and *14 were decreased in the DP-sensitive subjects compared with the controls (27.5% vs 45.5%, P = 0.002; 13.5% vs 24.2%, P = 0.02). Of the DRB1*04 alleles, DRB1*0403 was significantly decreased in the DP-sensitive subjects compared with the controls (3.9% vs 13.1%, P = 0.005). No significant differences were found in the distributions of the other HLA-DRB1 alleles between the two groups. CONCLUSION: HLA-DRB1*07 may have a susceptibility, and DRB1*04 and DRB1*14 may have a protective effect, upon the development of a sensitization to DP.

Adolescent↗
PubMed2000

H2O2-sensitive fur-like repressor CatR regulating the major catalase gene in Streptomyces coelicolor.

Streptomyces coelicolor produces three distinct catalases to cope with oxidative and osmotic stresses and allow proper growth and differentiation. The major vegetative catalase A (CatA) is induced by H(2)O(2) and is required for efficient aerobic growth. In order to investigate the H(2)O(2)-dependent regulatory mechanism, an H(2)O(2)-resistant mutant (HR40) overproducing CatA was isolated from S. coelicolor A3(2). Based on the genetic map location of the mutated locus in HR40, the wild type catR gene was isolated from the ordered cosmid library of S. coelicolor by screening for its ability to suppress the HR40 phenotype. catR encodes a protein of 138 amino acids (15319 Da), with sequence homology to ferric uptake regulator (Fur)-like proteins. Disruption of catR caused CatA overproduction as observed in the HR40 mutant, confirming the role of CatR as a negative regulator of catA expression. The levels of catA and catR transcripts were higher in HR40 than in the wild type, implying that CatR represses transcription of these genes. Transcripts from the catA and catR genes were induced within 10 min of H(2)O(2) treatment, suggesting that the repressor activity of CatR may be directly modulated by H(2)O(2). A putative CatR-binding site containing an inverted repeat of 23 base pairs was localized upstream of the catA and catR gene, on the basis of sequence comparison and deletion analysis. CatR protein purified in the presence of dithiothreitol bound to this region, whereas oxidized CatR, treated with H(2)O(2) or diamide, did not. The redox shift of CatR involved thiol-disulfide exchange as judged by modification of free thiols with 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonate. From these results we propose that CatR regulates its downstream target genes as a repressor whose DNA binding ability is directly modulated by redox changes in the cell.

Amino Acid Sequence↗
PubMed2000

Implication of a small GTPase Rac1 in the activation of c-Jun N-terminal kinase and heat shock factor in response to heat shock.

Heat shock induces c-Jun N-terminal kinase (JNK) activation as well as heat shock protein (HSP) expression through activation of the heat shock factor (HSF), but its signal pathway is not clearly understood. Since a small GTPase Rac1 has been suggested to participate in the cellular response to stresses, we examined whether Rac1 is involved in the heat shock response. Here we show that moderate heat shock (39-41 degrees C) induces membrane translocation of Rac1 and membrane ruffling in a Rac1-dependent manner. In addition, Rac1N17, a dominant negative mutant of Rac1, significantly inhibited JNK activation by heat shock. Since Rac1V12 was able to activate JNK, it is suggested that heat shock may activate JNK via Rac1. Similar inhibition by Rac1N17 of HSF activation in response to heat shock was observed. However, inhibitory effects of Rac1N17 on heat shock-induced JNK and HSF activation were reduced as the heat shock temperature increased. Rac1N17 also inhibited HSF activation by l-azetidine-2-carboxylic acid, a proline analog, and heavy metals (CdCl)), suggesting that Rac1 may be linked to HSF activation by denaturation of polypeptides in response to various proteotoxic stresses. However, Rac1N17 did not prevent phosphorylation of HSF1 in response to these proteotoxic stresses. Interestingly, a constitutively active mutant Rac1V12 did not activate the HSF. Therefore, Rac1 activation may be necessary, but not sufficient, for heat shock-inducible HSF activation and HSP expression, or otherwise a signal pathway(s) involving Rac1 may be indirectly involved in the HSF activation. In sum, we suggest that Rac1 may play a critical role(s) in several aspects of the heat shock response.

Animals↗
PubMed2000

First success of catalytic epoxidation of olefins by an electron-rich iron(III) porphyrin complex and H2O2: imidazole effect on the activation of H2O2 by iron porphyrin complexes in aprotic solvent.

An electron-rich iron(III) porphyrin complex (meso-tetramesitylporphinato)iron(III) chloride [Fe(TMP)Cl], was found to catalyze the epoxidation of olefins by aqueous 30% H2O2 when the reaction was carried out in the presence of 5-chloro-1-methylimidazole (5-Cl-1-Melm) in aprotic solvent. Epoxides were the predominant products with trace amounts of allylic oxidation products, indicating that Fenton-type oxidation reactions were not involved in the olefin epoxidation reactions. cis-Stilbene was stereospecifically oxidized to cis-stilbene oxide without giving isomerized trans-stilbene oxide product, demonstrating that neither hydroperoxy radical (HOO*) nor oxoiron(IV) porphyrin [(TMP)FeIV=O] was responsible for the olefin epoxidations. We also found that the reactivities of other iron(III) porphyrin complexes such as (meso-tetrakis(2,6-dichlorophenyl)porphinato)iron(III) chloride [Fe(TDCPP)Cl], (meso-tetrakis(2,6-difluorophenyl)porphinato)iron(III) chloride [Fe(TDFPP)Cl], and (meso-tetrakis(pentafluorophenyl)porphinato)iron(III) chloride [Fe(TPFPP)CI] were significantly affected by the presence of the imidazole in the epoxidation of olefins by H2O2. These iron porphyrin complexes did not yield cyclohexene oxide in the epoxidation of cyclohexene by H2O2 in the absence of 5-Cl-1-MeIm in aprotic solvent; however, addition of 5-Cl-1-MeIm to the reaction solutions gave high yields of cyclohexene oxide with the formation of trace amounts of allylic oxidation products. We proposed, on the basis of the results of mechanistic studies, that the role of the imidazole is to decelerate the O-O bond cleavage of an iron(III) hydroperoxide porphyrin (or H2O2-iron(II) porphyrin adduct) and that the intermediate transfers its oxygen to olefins prior to the O-O bond cleavage.

Alkenes↗
PubMed2000

A method for parameter optimization in computational biology.

Models in computational biology, such as those used in binding, docking, and folding, are often empirical and have adjustable parameters. Because few of these models are yet fully predictive, the problem may be nonoptimal choices of parameters. We describe an algorithm called ENPOP (energy function parameter optimization) that improves-and sometimes optimizes-the parameters for any given model and for any given search strategy that identifies the stable state of that model. ENPOP iteratively adjusts the parameters simultaneously to move the model global minimum energy conformation for each of m different molecules as close as possible to the true native conformations, based on some appropriate measure of structural error. A proof of principle is given for two very different test problems. The first involves three different two-dimensional model protein molecules having 12 to 37 monomers and four parameters in common. The parameters converge to the values used to design the model native structures. The second problem involves nine bumpy landscapes, each having between 4 and 12 degrees of freedom. For the three adjustable parameters, the globally optimal values are known in advance. ENPOP converges quickly to the correct parameter set.

Algorithms↗
PubMed2000

The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis.

OBJECTIVE: The purpose of this study was to determine whether funisitis (inflammation of the umbilical cord detected by histologic examination of the placenta) is associated with changes in the umbilical cord plasma concentration of interleukin 6, microbial invasion of the amniotic cavity, and neonatal sepsis. STUDY DESIGN: The relationship among the presence of funisitis, interleukin 6 concentrations in umbilical cord plasma at birth, the results of amniotic fluid culture performed within 3 days of birth, and the occurrence of congenital neonatal sepsis was examined in 315 consecutive singleton preterm births (20-35 weeks' gestation). Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. The interleukin 6 concentration was measured with a specific immunoassay. Amniocentesis was performed in 106 patients within 3 days of birth. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. RESULTS: (1) Funisitis was present in 25% of patients (78/315). (2) Patients with funisitis had a significantly higher median cord plasma interleukin 6 and a lower gestational age at birth than did those without funisitis (cord interleukin 6: median, 52.4 pg/mL; range, 0.9-19,230 pg/mL; vs median, 4.6 pg/mL; range, 0-18,108 pg/mL; gestational age: median, 31.1 weeks' gestation; range, 21.0-35.0 weeks' gestation; vs median, 32.9 weeks' gestation; range, 21.4-35.0 weeks' gestation; P<.001 for each comparison). (3) A cord plasma interleukin 6 of > or =17.5 pg/mL had a sensitivity of 70% and a specificity of 78% in the identification of funisitis. (4) Microbial invasion of the amniotic cavity and clinical chorioamnionitis were more common among patients with funisitis than among those without funisitis (positive amniotic fluid culture: 53% [20/38]; vs. 12% [8/68]; clinical chorioamnionitis: 18% [14/78]; vs. 4% [9/237]; P<.001 for each comparison). (5) Neonates with funisitis had a significantly higher rate of congenital sepsis than did those without this lesion (12% [8/66] vs. 1% [3/216]; P<.001); this difference remained significant after adjustment for gestational age at birth (odds ratio, 7.2; 95% confidence interval, 1.8-29.0). CONCLUSION: (1) Umbilical cord plasma interleukin 6 concentrations were higher in neonates born with funisitis than in those without this lesion. (2) Funisitis is associated with amniotic fluid infection, congenital neonatal sepsis, and the fetal inflammatory response syndrome.

Adult↗
PubMed2000

Regulation of the furA and catC operon, encoding a ferric uptake regulator homologue and catalase-peroxidase, respectively, in Streptomyces coelicolor A3(2).

We isolated the catC gene, encoding catalase-peroxidase in Streptomyces coelicolor, using sequence homology with the katG gene from Escherichia coli. Upstream of the catC gene, an open reading frame (furA) encoding a homologue of ferric uptake regulator (Fur) was identified. S1 mapping analysis indicated that the furA gene was cotranscribed with the catC gene. The transcriptional start site of the furA-catC mRNA was mapped to the translation start codon ATG of the furA gene. The putative promoter contains consensus -10 and -35 elements similar to those recognized by sigma(HrdB), the major sigma factor of S. coelicolor. The transcripts were produced maximally at late-exponential phase and decreased at the stationary phase in liquid culture. The change in the amount of mRNA was consistent with that of CatC protein and enzyme activity. When the furA gene was introduced into S. lividans on a multicopy plasmid, the increased production of catC transcripts and protein product at late growth phase was inhibited, implying a role for FurA as the negative regulator of the furA-catC operon. FurA protein bound to its own promoter region between -59 and -39 nucleotides from the transcription start site. The binding affinity of FurA increased under reducing conditions and in the presence of metals such as Ni(2+), Mn(2+), Zn(2+), or Fe(2+). Addition of these metals to the growth medium decreased the production of CatC protein, consistent with the role of FurA as a metal-dependent repressor.

Amino Acid Sequence↗