GDF15 is a potential predictive biomarker for TPF induction chemotherapy and promotes tumorigenesis and progression in oral squamous cell carcinoma.

BACKGROUND: Randomized trials have not shown major survival benefits when induction chemotherapy plus standard therapy is compared with standard therapy alone in patients with oral squamous cell carcinoma (OSCC). Induction chemotherapy is likely to be effective for biologically distinct subgroups and biomarker development may lead to identification of patients whose tumors are likely to respond to a particular treatment. PATIENTS AND METHODS: We evaluated immunohistochemical staining for GDF15 in pretreatment biopsy specimens of 230 of 256 OSCC patients who were treated in a prospective, randomized, phase III trial on induction chemotherapy including docetaxel, cisplatin and 5-fluorouracil (TPF). Relationship between GDF15 intervention and cell proliferation, migration, invasion, colony formation and tumorigenicity was analyzed using in vitro and in vivo OSCC models. RESULTS: Low GDF15 expression predicted a better survival in OSCC patients, especially overall survival [P = 0.049, hazard ratio (HR) = 0.597] and distant metastasis-free survival (DMFS; P = 0.031, HR = 0.562). cN+ patients with low GDF15 expression benefitted from induction TPF in overall survival (P = 0.039, HR = 0.247) and DMFS (P = 0.039, HR = 0.247), cN- patients with high GDF15 expression benefitted from induction TPF in overall survival (P = 0.019, HR = 0.231), disease-free survival (P = 0.011, HR = 0.281), locoregional recurrence-free survival (P = 0.035, HR = 0.347) and DMFS (P = 0.009, HR = 0.197). Decreased GDF15 expression in OSCC lines significantly inhibited cell proliferation, migration, invasion, colony formation and tumorigenesis through increased phosphorylation of AKT and ERK1/2 (P < 0.05). Likewise, overexpression of GDF15 significantly promoted cell proliferation, migration, invasion and colony formation through decreased phosphorylation of AKT and ERK1/2 (P < 0.05). CONCLUSIONS: GDF15 expression can be used as a prognostic biomarker for OSCC, and as a predictive biomarker for benefitting from TPF induction chemotherapy. GDF15 promotes tumorigenesis and progression through phosphorylation of AKT and ERK1/2 in OSCC. The clinical trial in this study was registered with www.ClinicalTrials.gov (NCT01542931).

[A study on knowledge, attitude, and vaccination behavior of herpes zoster vaccine among urban residents in selected areas of China].

Objective: To understand the knowledge, attitude, and current status of vaccination of herpes zoster vaccination among urban residents aged 25 years and above in China. Methods: In August to October 2022, a convenience sampling method was used to survey residents aged 25 years and above at 36 community centers in 9 cities across China. Questionnaires were used to collect basic information, knowledge, and attitude toward herpes zoster and its vaccination, as well as vaccination status and reasons for non-vaccination among residents. Results: A total of 2 864 urban residents were included in the study. The total score of residents' cognition of herpes zoster and its vaccine was 3.01±2.08, and the total score of their attitude was 18.25±2.76. Factors such as being male (ß=-0.45, P<0.001), older than 40-59 years (ß=-0.34, P=0.023) or ≥60 years (ß=-0.68, P<0.001), married (ß=-0.69, P=0.002) were negatively associated with knowledge score. The educational level of high school or secondary school (ß=0.44, P=0.036), college (ß=0.65, P=0.006), bachelor's degree and above (ß=1.20, P<0.001), annual net household income ≥120 000 Yuan in 2021 (ß=0.42, P=0.020), having urban employee medical insurance (ß=0.62, P=0.030), having public or commercial medical insurance (ß=0.65, P=0.033), and having a history of chickenpox (ß=0.29, P=0.025) were positively associated with knowledge scores. Being male (ß=-0.38, P=0.008) and not remembering a history of chickenpox (ß=-0.49, P=0.012) were negatively associated with attitude scores. Annual net household income in 2021 was between 40 000-80 000 Yuan (ß=0.44, P=0.032) or between 80 000-120 000 Yuan (ß=0.62, P=0.002) or ≥120 000 Yuan (ß=0.93, P<0.001), and a history of herpes zoster (ß=0.59, P=0.004) were positively associated with attitude scores. Of the 2 864 residents surveyed, only 29 (1.01%) had received the herpes zoster vaccine, with a vaccination rate of 1.70% for those aged 50 years and above, with the main reason for non-vaccination being lack of knowledge about the herpes zoster vaccine, followed by the high price. 42.67% of the population said they would consider getting the herpes zoster vaccine in the future. Conclusion: Low knowledge of herpes zoster and its vaccine, positive attitudes towards the preventive effects of herpes zoster and its vaccine, and extremely low vaccination rates among the urban population in China call for multiple measures to strengthen health education and vaccination recommendations for residents, especially for the elderly, low-education and low-income populations.

Cinnamomin: separation, crystallization and preliminary X-ray diffraction study.

Cinnamomin from Cinnamonum camphora seeds, a type II ribosome-inactivating protein that interferes with protein biosynthesis in mammalian cells, can induce the apoptosis of carcinoma cells and be used as an insecticide. A rapid and improved method has been developed for the extraction and purification of cinnamomin from camphora seed. Purification of cinnamomin is achieved with two successive steps of hydrophobic interaction chromatography carried out on a fast protein liquid chromatography (FPLC) system. Crystals suitable for X-ray diffraction analysis were obtained by vapor diffusion method. A complete data set at 2.8 A resolution has been collected. Data indexation and refinement indicate that the crystal is orthorhombic with space group P2(1)2(1)2(1) and unit cell dimensions a = 52.39 A, b = 126.33 A, c = 161.45 A. There are two molecules per asymmetric unit. Initial phasing by molecular replacement method yielded a solution, which will contribute to the structure determination. A molecular model will further the understanding of the mechanism of cinnamomin function. The latter will be combined with bio-informatics to facilitate the medical and other applications of cinnamomin.

[microRNA-146a reverses the inhibitory effects of Porphyromonas gingivalis lipopolysaccharide on osteogenesis of human periodontal ligament cells].

Objective: To investigate the effects and mechanisms of microRNA-146a (miR-146a) on osteogenic differentiation of human periodontal ligament cells (hPDLC) stimulated by lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg). Methods: hPDLC were cultured in vitro and induced to the phase of osteogenic differentiation. These cells were divided into five groups: non-osteogenic differentiation cells, osteogenic differentiation cells, osteogenic differentiation cells treated with Pg LPS, osteogenic differentiation cells treated with Pg LPS and miR-146a mimic, osteogenic differentiation cells treated with Pg LPS and miR-146a negative control. Osteogenic markers and mineralization were detected via quantitative real-time PCR (qPCR) and alizarin red staining, respectively. Meanwhile, non-radioactive transcription factor assay was applied to explore the nuclear activity of nuclear factor kappa B (NF-κB) p65 in nuclear extracts of hPDLC. Results: Compared with cells of osteogenic differentiation in non-LPS-stimulated groups, Pg LPS could decrease the markers of osteogenic differentiation of hPDLC such as collagen Ⅰ (Col-Ⅰ), alkaline phosphatase (ALP), Runt-related transcription factor-2 (RUNX2) and osteocalcin (OCN) (P<0.05), inhibit mineralization, and stimulate NF-κB p65 nuclear activity expression (non-LPS stimulated group: 1.023±0.217, LPS stimulated group: 6.252±0.613, P=0.008). However, compared with cells in Pg LPS/miR-146a negative control group, miR-146a increased Col-Ⅰ (P=0.007) and OCN (P=0.049) mRNA expression, rather than ALP (P=0.167) and RUNX2 (P=0.580) at day 3; miR-146a also upregulated mRNA levels of Col-Ⅰ, ALP, RUNX2 and OCN (P<0.05) at day 7 and day 14, and enhance mineralization. Meanwhile, miR-146a mimic could decrease the nuclear activity of NF-κB p65 induced by Pg LPS in hPDLC (miR-146a: 2.427±0.354, negative control: 5.863±0.482, P=0.019). Conclusions: miR-146a could reverse the inhibitory effects of Pg LPS on osteogenic differentiation of hPDLC through enhancing the expression of osteogenic markers and decreasing inflammatory pathway in hPDLC.

Structural basis of the multispecificity demonstrated by 17beta-hydroxysteroid dehydrogenase types 1 and 5.

17Beta-hydroxysteroid dehydrogenases/ketosteroid reductases (17beta-HSDs/KSRs) catalyze the last step of sex steroid synthesis or the first step of their degradation, and are thus critical for many physiological processes. The multispecificity demonstrated by 17beta-HSDs is important for steroid metabolism in gonadal and peripheral tissues, and is a consequence of the architecture of their binding and catalytic sites. Structurally, most of the family members are short chain dehydrogenase-reductases (SDRs) except the type 5 enzyme, which is an aldo-keto reductase (AKR). 17Beta-HSD type 1, a representative of the SDR family, has been studied extensively since the 1950s. However, its structure was not determined until the 1990s. It has always been considered as estrogen specific, in accord with the narrow binding tunnel that has been structurally determined and has been found to be complementary to estrogens. A recent study revealed that, in spite of the enzyme's narrow binding tunnel, the pseudo-symmetry of C19 steroids leads to its alternative binding, resulting in the multispecificity of the enzyme. Expressed in ovary, breast and placenta, the enzyme catalyzes the formation of another estrogen A-diol from DHEA in addition to the biosynthesis of estradiol; it also inactivates the most active androgen DHT by both 17beta-hydroxysteroid oxidation and 3-ketosteroid reduction. Type 5 17beta-HSD (AKR1C3) differs significantly from the type 1 enzyme by possessing a spacious and flexible steroid-binding site. This is estimated to be about 960 or 470 A3 in ternary complex with testosterone or 4-dione, respectively, whereas the binding site volume of 17beta-HSD1 is only about 340 A3. This characteristic of the 17beta-HSD5 binding site permits the docking of various steroids in different orientations, which encompasses a wider range of activities from 20alpha-, 17beta- and 3alpha-HSD/KSR to prostaglandin 11-ketoreductase. The in vitro activities of the enzyme are significantly lower than the type 1 enzyme. In the ternary complex with testosterone, the steroid C3-C17 position is quasi-reversed as compared to the complex with 4-dione. The multi-specificity contributes significantly to steroid metabolism in peripheral tissues, due to the high levels of 17beta-HSD5 mRNA in both breast and prostate tissues.

Structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase at 2.20 A resolution.

BACKGROUND: The principal human estrogen, 17 beta-estradiol, is a potent stimulator of certain endocrine-dependent forms of breast cancer. Because human estrogenic 17 beta-hydroxysteroid dehydrogenase (type I 17 beta-HSD) catalyzes the last step in the biosynthesis of 17 beta-estradiol from the less potent estrogen, estrone, it is an attractive target for the design of inhibitors of estrogen production and tumor growth. This human enzyme shares less than 15% sequence identity with a bacterial 3 alpha,20 beta-HSD, for which the three-dimensional structure is known. The amino acid sequence of 17 beta-HSD also differs from that of bacterial 3 alpha,20 beta-HSD by two insertions (of 11 and 14 residues) and 52 additional residues at the C terminus. RESULTS: The 2.20 A resolution structure of type I 17 beta-HSD, the first mammalian steroidogenic enzyme studied by X-ray crystallographic techniques, reveals a fold characteristic of the short-chain dehydrogenases. The active site contains a Tyr-X-X-X-Lys sequence (where X is any amino acid) and a serine residue, features that are conserved in short-chain steroid dehydrogenases. The structure also contains three alpha-helices and a helix-turn-helix motif, not observed in short-chain dehydrogenase structures reported previously. No cofactor density could be located. CONCLUSIONS: The helices present in 17 beta-HSD that were not in the two previous short-chain dehydrogenase structures are located at one end of the substrate-binding cleft away from the catalytic triad. These helices restrict access to the active site and appear to influence substrate specificity. Modeling the position of estradiol in the active site suggests that a histidine side chain may play a critical role in substrate recognition. One or more of these helices may also be involved in the reported association of the enzyme with membranes. A model for steroid and cofactor binding as well as for the estrone to estradiol transition state is proposed. The structure of the active site provides a rational basis for designing more specific inhibitors of this breast cancer associated enzyme.

Radiofrequency catheter ablation for management of symptomatic ventricular ectopic activity.

OBJECTIVES: This study assessed the useful role of intracardiac mapping and radiofrequency catheter ablation in eliminating drug-refractory monomorphic ventricular ectopic beats in severely symptomatic patients. BACKGROUND: Ventricular ectopic activity is commonly encountered in clinical practice. Usually, it is not associated with life-threatening consequences in the absence of significant structural heart disease. However, frequent ventricular ectopic beats can be extremely symptomatic and even incapacitating in some patients. Currently, reassurance and pharmacologic therapy are the mainstays of treatment. There has been little information on the use of catheter ablation in such patients. METHODS: Ten patients with frequent and severely symptomatic monomorphic ventricular ectopic beats were selected from three tertiary care centers. The mean frequency +/- SD of ventricular ectopic activity was 1,065 +/- 631 beats/h (range 280 to 2,094) as documented by baseline 24-h ambulatory electrocardiographic (ECG) monitoring. No other spontaneous arrhythmias were documented. These patients had previously been unable to tolerate or had been unsuccessfully treated with a mean of 5 +/- 3 antiarrhythmic drugs. The site of origin of ventricular ectopic activity was accurately mapped by using earliest endocardial activation time during ectopic activity or pace mapping, or both. RESULTS: During electrophysiologic study, no patient had inducible ventricular tachycardia. The ectopic focus was located in the right ventricular outflow tract in nine patients and in the left ventricular posteroseptal region in one patient. Frequent ventricular ectopic beats were successfully eliminated by catheter-delivered radiofrequency energy in all 10 patients. The mean number of radiofrequency applications was 2.6 +/- 1.3 (range 1 to 5). No complications were encountered. During a mean follow-up period of 10 +/- 4 months, no patient had a recurrence of symptomatic ectopic activity, and 24-h ambulatory ECG monitoring showed that the frequency of ventricular ectopic activity was 0 beat/h in seven patients, 1 beat/h in two patients and 2 beats/h in one patient. CONCLUSIONS: Radiofrequency catheter ablation can be successfully used to eliminate monomorphic ventricular ectopic activity. It may therefore be a reasonable alternative for the treatment of severely symptomatic, drug-resistant monomorphic ventricular ectopic activity in patients without significant structural heart disease.

Crystallization and preliminary X-ray diffraction analysis of the complex of human placental 17 beta-hydroxysteroid dehydrogenase with NADP+.

Single crystals of human placental 17 beta-hydroxysteroid dehydrogenase, an enzyme that plays an important role in the interconversion of estrogens, were obtained as the NADP+ complex. These are the first crystals suitable for complete X-ray structure analysis ever reported for a steroid-converting enzyme from a human source. The crystals were grown by vapor diffusion at pH 7.5 with polyethyleneglycol (4000) as the precipitating agent. They have a monoclinic space group C2 and unit cell parameters are a = 123.03 A, b = 45.03 A, c = 61.29 A, and beta = 99.1 degrees. A complete set of diffraction data to 2.9 A has been collected on native crystals.

Studies on the three-dimensional structure of estrogenic 17 beta-hydroxysteroid dehydrogenase.

The structure-function relationship of the estrogenic 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD1), a pivotal enzyme in the synthesis of active sex hormones, has been studied via protein chemistry and crystallography. A highly active and homogeneous 17 beta-HSD1 was prepared with a rapid purification from human placenta. We then characterized the native and expressed enzyme, and concluded, for the first time, that 17 beta-HSD1 is formed by two identical subunits. The enzyme was also overproduced in insect cells with a baculovirus expression system. The highly active 17 beta-HSD1 preparation was successfully crystallized in the presence of NADP-, polyethylene glycol, beta-octylglucoside and glycerol, resulting in the first diffraction quality crystals of any steroid-converting enzyme from a human source. The three-dimensional structure of 17 beta-HSD1 was determined at 2.2 A resolution, showing that the overall structure of the enzyme is similar to the other enzymes in the short-chain dehydrogenase family, with a conserved Tyr-X-X-X-Lys sequence and a serine residue in the active site. It is distinguished from the other known structures reported for short-chain dehydrogenases by the insertion of two helix-turn-helix motifs that appear to govern membrane association and substrate specificity [corrected]. More recently, the complex of 17 beta-HSD1 with estradiol has been successfully crystallized and its structure determined. The latter demonstrates detailed information of the interactions between the substrate and residues Ser142, Tyr155, His221 and Glu282 of the enzyme. These interactions and the complementarity of the substrate with the hydrophobic binding pocket make critical contributions to the enzyme specificity. The above results provide a strong basis for the design of potent inhibitors of this pivotal steroid dehydrogenase.

Crystallization and preliminary crystal structure of the complex of 17beta-hydroxysteroid dehydrogenase with a dual-site inhibitor.

Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1) catalyzes the synthesis of 17beta-estradiol (E2) from estrone, in the ovary and peripheral tissues. While the structures of 17beta-HSD1 alone and in complex with E2 have been determined (D. Ghosh, V. Pletnev, D.-W. Zhu, Z. Wawrzak, W.-L. Duax, W. Pangborn, F. Labrie, S.-X. Lin, Structure of human 17beta-hydroxysteroid dehydrogenase at 2.20 A resolution, Structure 3 (1995) 503-513), no structures of inhibitor/enzyme complex, either modeled or from crystallography, have been reported before the submission of the present paper. The best available inhibitors are among the 'dual-site inhibitors', blocking estrogenic 17beta-HSD and the estrogen receptor. These compounds belong to a family of estradiol analogues having an halogen atom at the 16alpha position and an extended alkyl-amide chain at the 7alpha position (C. Labrie, G. Martel, J.M. Dufour, G. Levesque, Y. Merand, F. Labrie, Novel compounds inhibit estrogen formation and action, Cancer Res. 52 (1992) 610-615). We now report the crystallization of this enzyme/inhibitor complex. The complex of the best available dual-site inhibitor, EM-139, with 17beta-HSD1 has been crystallized using both cocrystallization and soaking methods. Crystals are isomorphous to the native crystals grown in the presence of 0.06% beta-octyl-glucoside and polyethyleneglycol 4000, with a monoclinic space group C2. Data at 1.8 A have been collected from a synchrotron source. Even though the size of the inhibitor is greater than that of the substrate, our preliminary X-ray-diffraction study shows that EM-139 fits into the active site in a position similar to that of estrogen. The availability of such structural data will help design more potent inhibitors of estrogenic 17beta-HSD.

Human 17 beta-hydroxysteroid dehydrogenase: optical properties of its complex with NADP+.

The apoenzyme of the human placental 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and its complex with NADP+ were prepared from two alternative procedures. The apoenzyme (Form I) has an absorption maximum at about 279 nm, and an absorption ratio at 280 and 260 nm of 1.65 +/- 0.1; whereas the complex (Form II) has a broad absorption peak between 268-278 nm, and a 280 to 260 nm ratio of 1.1 +/- 0.05. Upon addition of the substrate estradiol to the complex, an absorption increase at 340 nm and a fluorescence emission at 450 nm, following NADPH formation, were produced. Both changes indicate that one cofactor is tightly bound to the 17 beta-HSD molecule in this complex. No significant optical change can be produced in this way for the apoenzyme. Convenient analyses of cofactor content of the enzyme are thus provided. The optical analyses and the homogeneous apo- or holo-enzyme preparations are important in the study of the enzyme's function and crystallization. This is the first human steroid converting enzyme which has yielded X-ray quality crystals.

3D-structure of human estrogenic 17beta-HSD1: binding with various steroids.

Human estrogenic dehydrogenase (17beta-HSD1) catalyses the last step in the biosynthesis of the active estrogens that stimulate the proliferation of breast cancer cells. While the primary substrate for the enzyme is estrone, the enzyme has some activity for the non-estrogenic substrates. To better understand the structure function relationships of 17beta-HSD1 and to provide a better ground for the design of inhibitors, we have determined the crystal structures of 17beta-HSD1 in complex with different steroids. The structure of the complex of estradiol with the enzyme determined previously (Azzi et al., Nature Structural Biology 3, 665-668) showed that the narrow active site was highly complementary to the substrate. The substrate specificity is due to a combination of hydrogen bonding and hydrophobic interactions between the steroid and the enzyme binding pocket. We have now determined structures of 17beta-HSD1 in complex with dihydrotestosterone and 20alpha-OH-progesterone. In the case of the C19 androgen, several residues within the enzyme active site make some small adjustments to accommodate the increased bulk of the substrate. In addition, the C19 steroids bind in a slightly different position from estradiol with shifts in positions of up to 1.4 A. The altered binding position avoids unfavorable steric interactions between Leu 149 and the C19 methyl group (Han et al., unpublished). The known kinetic parameters for these substrates can be rationalized in light of the structures presented. These results give evidence for the structural basis of steroid recognition by 17beta-HSD1 and throw light on the design of new inhibitors for this pivotal steroid enzyme.

Two non-reactive ternary complexes of estrogenic 17beta-hydroxysteroid dehydrogenase: crystallization and preliminary structural analysis.

Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1, EC1.1.1.62) is an important enzyme that catalyses the last step of active estrogen formation. 17Beta-HSD1 plays a key role in the proliferation of breast cancer cells. The three-dimensional structures of this enzyme and of the enzyme-estradiol complex have been solved (Zhu et al., 1993, J. Mol. Biol. 234:242; Ghosh et al., 1995, Structure 3:503; Azzi et al., 1996, Nature Struct. Biol. 3:665). The determination of the non-reactive ternary complex structure, which could mimic the transition state, constitutes a further critical step toward the rational design of inhibitors for this enzyme (Ghosh et al. 1995, Structure 3:503; Penning, 1996, Endocrine-Related Cancer, 3:41). To further study the transition state, two non-reactive ternary complexes, 17beta-HSD1-EM519-NADP+ and 17beta-HSD1-EM553-NADP+ were crystallized using combined methods of soaking and co-crystallization. Although they belong to the same C2 space group, they have different unit cells, with a = 155.59 A, b = 42.82 A, c = 121.15 A, beta = 128.5 degrees for 17beta-HSD1-EM519-NADP+, and a = 124.01 A, b = 45.16 A, c = 61.40 A, beta = 99.2 degrees for 17beta-HSD1-EM553-NADP+, respectively. Our preliminary results revealed that the inhibitors interact differently with the enzyme than do the natural substrates.

Case report: radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia in a patient with heart transplantation.

Ten years after orthotopic cardiac transplantation, a 56-year-old man developed recurrent presyncope and syncope. A 24-hour ambulatory electrocardiographic recording did not document significant arrhythmic events. A head-up tilt table test was negative. An electrophysiologic study revealed dual atrioventricular (AV) nodal physiology and inducible typical atrioventricular nodal reentrant tachycardia (AVNRT). The patient became hypotensive and presyncopal during AVNRT. Radiofrequency (RF) catheter ablation successfully eliminated AVNRT without complications. The patient remained free of symptoms at nine months follow-up.

Pacing therapy for atrial tachyarrhythmias.

The use of pacing techniques for the treatment of atrial tachyarrhythmias has been advocated for more than 30 years. Although it has played a beneficial role in the management of paroxysmal supraventricular tachycardia (PSVT) in drug-refractory patients, tachycardia acceleration and development of atrial fibrillation has been the major drawback. With the availability of radiofrequency catheter ablation therapy, the use of implantable antitachycardia devices for PSVT is currently negligible. From retrospective and small control studies it has been shown that atrial or dual-chamber pacing in patients with sick sinus syndrome has been associated with a lower incidence of paroxysmal atrial flutter or fibrillation than in those who received a ventricular pacemaker. Furthermore, recent studies have reported the potential benefit of reducing frequency of paroxysmal atrial flutter and fibrillation with multisite atrial pacing. As a result, there is a resurgence of research interest in antitachycardia pacing for prevention of atrial tachyarrhythmias. This paper briefly describes the basic aspects of antitachycardia pacing, reviews the data on the use of implantable antitachycardia devices for PSVT and the selection of patients, and assesses the current status of research on atrial pacing for prevention of paroxysmal atrial flutter and fibrillation.

Solid-phase photocatalytic degradation of polyethylene-goethite composite film under UV-light irradiation.

A novel photodegradable polyethylene-goethite (PE-goethite) composite film was prepared by embedding the goethite into the commercial polyethylene. The degradation of PE-goethite composite films was investigated under ultraviolet light irradiation. The photodegradation activity of the PE plastic was determined by monitoring its weight loss, scanning electron microscopic (SEM) analysis and FT-IR spectroscopy. The weight of PE-goethite (1 wt%) sample steadily decreased and led to the total 16% reduction in 300 h under UV-light intensity for 1 mW/cm(2). Through SEM observation there were some cavities around the goethite powder in the composite films, but there were few changes except some surface chalking phenomenon in pure PE film. The degradation rate could be controlled by changing the concentration of goethite particles in PE plastic. The degradation of composite plastic initiated on PE-goethite interface and then extended into polymer matrix induced by the diffusion of the reactive oxygen species generated on goethite particle surface. The photocatalytic degradation mechanism of the composite films was briefly discussed.

Attempts to rationalize protein crystallization using relative crystallizability.

Protein crystal growth (PCG) remains the bottleneck of crystallography despite many decades of study. The nucleation zone in the two-dimensional-phase diagram has been used to evaluate the relative crystallizability of proteins, which is expressed as a percentage over the phase area delineated by experimental protein and precipitating agent concentration ranges. For protein-salts which are subject to a direct temperature effect on solubility, as represented by Egg Lysozyme, a decrease in temperature augments the nucleation zone percentage whereas for those with retrograde solubility as a function of temperature, for example fructose-1,6-bisphosphatase in the presence and absence of AMP, an increase in temperature can significantly enhance the relative crystallizability. These results have been confirmed by the number of "hits" using PEGs as precipitating agents in Sparse Matrix Screen experiments for different proteins and are in excellent agreement with the relative crystallizability. The relationship between solubility dependence, relative crystallizability and crystallization success, has been evidenced. Such crystallizability can become a guide to identify efficient crystallization regions, providing a rational approach to PCG and structural biology.

The value of electrophysiology study and prophylactic implantation of cardioverter defibrillator in patients with hypertrophic cardiomyopathy.

Fifty-three consecutive patients with hypertrophic cardiomyopathy (HCM) and no history of sudden death underwent electrophysiology (EP) study. Sustained polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF) was induced in 19 patients (35%). Patients with prior syncope or near syncope had a higher incidence of VT/VF inducibility. An implantable cardioverter defibrillator (i.c.d.) was placed in 14 of the 19 patients. Of the remaining 5 patients with inducible VT/VF, three refused ICD implantation, while two underwent septal myectomy and VT/VF was no longer inducible after the operation. None of the patients received antiarrhythmic drugs. During a mean follow-up period of 47 +/- 31 (2-117) months, no events occurred in the 34 patients with negative EP study. Three events occurred among the 19 patients with inducible VT/VF. One patient died suddenly, one developed wide complex tachycardia which required resuscitation, and one patient received an appropriate ICD shock. In conclusion, sustained polymorphic VT/VF was inducible in about one-third of patients with HCM. Noninducibility of VT/VF appeared to predict a favorable prognosis. Although the overall event rate was low in patients with inducible VT/VF, prophylactic ICD implantation in patients with multiple risk factors may be appropriate.

Atrial septal pacing: a method for pacing both atria simultaneously.

By pacing both atria simultaneously, one could reliably predict and optimize left-sided AV timing without concern for IACT. With synchronous depolarization of the atria, reentrant arrhythmias might be suppressed. We studied four male patients (73 +/- 3 years) with paroxysmal atrial fibrillation and symptomatic bradyarrhythmias using TEE and fluoroscopy as guides; a standard active fixation screw-in lead (Medtronic model #4058) was attached to the interatrial septum and a standard tined lead was placed in the ventricle. The generators were Medtronic model 7960. The baseline ECG was compared to the paced ECG and the conduction time were measured to the high right atrium, distal coronary sinus and atrial septum in normal sinus rhythm, atrial septal pacing, and AAT pacing. On the surface ECG, no acceleration or delay in AV conduction was noted during AAI pacing from the interatrial septum as compared with normal sinus rhythm. The mean interatrial conduction time for all 4 patients was 106 +/- 2 ms; the interatrial conduction time measured during AAT pacing utilizing the atrial septal pacing lead was 97 +/- 4 ms (P = NS). During atrial septal pacing, the mean conduction time to the high right atrium was 53 +/- 2 ms. The mean conduction time to the lateral left atrium during atrial septal pacing, was likewise 53 +/- 2 ms. We conclude that it is possible to pace both atria simultaneously from a single site using a standard active fixation lead guided by TEE and fluoroscopy. Such a pacing system allows accurate timing of the left-sided AV delay.