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PubMed2006

De novo design of monomeric beta-hairpin and beta-sheet peptides.

Since the first report in 1993 (JACS 115, 5887-5888) of a peptide able to form a monomeric beta-hairpin structure in aqueous solution, the design of peptides forming either beta-hairpins (two-stranded antiparallel beta-sheets) or three-stranded antiparallel beta-sheets has become a field of intense interest. These studies have yielded great insights into the principles governing the stability and folding of beta-hairpins and antiparallel beta-sheets. This chapter reviews briefly those principles and describes a protocol for the de novo design of beta-sheet-forming peptides based on them. Criteria to select appropriate turn and strand residues and to avoid aggregation are provided. Because nuclear magnetic resonance is the most appropriate technique to check the success of new designs, the nuclear magnetic resonance parameters characteristic of beta-hairpins and three-stranded antiparallel beta-sheets are given.

Peptides↗
PubMed2000

Stabilized subcutaneous ulnar nerve transposition with immediate range of motion. Long-term follow-up.

BACKGROUND: Anterior transposition of the ulnar nerve at the elbow produces generally good results regardless of whether the nerve is transposed subcutaneously, intramuscularly, or submuscularly. The eventual recovery of nerve function is related less to the specific surgical technique than to the severity of the intrinsic nerve pathology. A primary variable in surgical management is the duration of postoperative elbow immobilization. The purpose of this study was to review the longterm results of a specific technique of subcutaneous anterior transposition of the ulnar nerve that utilizes a stabilizing fasciodermal sling. The study compared the results of immediate and late institution of a range of motion postoperatively. METHODS: Forty-seven patients with fifty-one elbows were reexamined, by an investigator who had not been involved in their treatment, at a minimum of two years (range, twenty-four months to fourteen years) after an anterior transposition. Of the fifty-one elbows, twenty-one were immobilized for two to three weeks whereas thirty were managed with an immediate range of motion. RESULTS: At the latest follow-up evaluation, there were occasional, mild paresthesias in 16 percent of the limbs and there was still subjective weakness of 19 percent. Both pinch and grip strength had increased substantially. No patient had lost elbow motion. A positive Tinel sign persisted in 31 percent of the limbs, but it was mildly positive in most of them. The elbow flexion test was uniformly negative. The results for 92 percent of the limbs were satisfactory to the patients, who stated that they would undergo the same procedure again if necessary. Overall, 73 percent of the limbs had an excellent result; 18 percent, a good result; 4 percent, a fair result; and 6 percent, a poor result. With the numbers available, no significant difference could be detected, with regard to these outcomes, between the group managed with elbow immobilization and that managed with immediate elbow mobilization. However, patients treated with a postoperative cast returned to work at an average of thirty days after surgery whereas the group treated with immediate motion of the elbow returned to work at an average of ten days. CONCLUSIONS: This technique of stabilized subcutaneous anterior transposition of the ulnar nerve yielded predictably good results for a wide spectrum of patients. Patients returned to their occupation sooner when the elbow had been mobilized immediately.

Adult↗
PubMed2006

Experimental study on sludge reduction by ultrasound.

In recent years, considerable impetus emerges to develop strategies for reducing excess sludge produced in biological wastewater treatment (BWT) systems. In this study, an experiment on sludge reduction by ultrasound treatment was conducted. The influences of sonication on observed yield, sludge reduction, effluent quality, sludge settleability and stability were extensively evaluated. It was found that ultrasound had an impressive potential to reduce sludge production. Moreover, it was also concluded that a treatment time of 10 minutes was more cost-effective for sludge reduction, and a reduction by 44% was reached with an ultrasonic intensity of 0.25 w/ml. The reduction could be mainly attributed to disintegration of bio-flocs and cryptic growth. In addition, sonication time seemed to be more effective to reduce sludge production compared with ultrasonic intensity. Slight deterioration of the effluent quality and some variations of the sludge settleability and stability were observed after ultrasound treatment.

Ammonia↗
PubMed1999

Biodistribution study of 188Re-labeled trisuccin-HuCC49 and trisuccin-HuCC49deltaCh2 conjugates in athymic nude mice bearing intraperitoneal colon cancer xenografts.

The trihydroxamate bifunctional chelating agent (BCA), trisuccin, has been shown to be a potential ligand for radiolabeling of monoclonal antibodies (MAbs) with rhenium radioisotopes, through an indirect postconjugation approach. The use of this trihydroxamate BCA made it possible to prepare stable BCA-MAb conjugates in pure form that could be radiolabeled with carrier-free 188Re. The anti-TAG-72 murine MAb, CC49, and its humanized derivatives are promising agents in the treatment of a number of malignancies with the CH2 domain-deleted MAb (HuCC49deltaCH2), which is of particular interest due to its rapid blood clearance. The biodistribution of 188Re-labeled conjugates of trisuccin with both humanized CC49 (HuCC49) and HuCC49deltaCH2 in athymic nude mice implanted i.p. with LS174T human colon carcinoma was studied. Trisuccin-MAb conjugates were synthesized at different BCA:MAb ratios by the 6-oxoheptanoic acid method using trisuccin hydrazide. The conjugates were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy for the number of incorporated trisuccin molecules. The conjugates were radiolabeled with carrier-free, generator-produced 188Re and purified by gel filtration on Sephadex G-25. Labeling yields and homogeneity of the labeled conjugates were analyzed by high-pressure liquid chromatography and instant TLC. Athymic nude mice were injected i.p. with LS174T human colon carcinoma cells, 7 days prior to injection of the labeled antibodies. 188Re-labeled MAbs were injected i.p., and the mice were sacrificed 24 h postinjection. Matrix-assisted laser desorption/ionization time-of-flight analyses showed stable incorporation of trisuccin into each MAb, with the measured ligand:MAb values positively correlating with the theoretical ratios. Labeling of the conjugates with 188Re proceeded with high yields, producing homogeneous 188Re-MAbs with good stabilities as shown by instant TLC and biodistribution analyses. Biodistribution of the radiolabeled MAbs at 24 h after injection showed median tumor uptake values of 23.5%ID/g and 17.6%ID/g for the 188Re-HuCC49deltaCH2 and 188Re-HuCC49, respectively. The blood clearance of the domain-deleted MAb was faster than that of the intact antibody. The blood values at 24 h after injection were 0.7%ID/g for 188Re-HuCC49deltaCH2 and 3.2%ID/g for 188Re-HuCC49. The results indicate that trisuccin is a promising agent for postconjugation labeling of antibodies with 188Re. Additionally, these results illustrate the potential of 188Re-HuCC49deltaCH2 in radioimmunodiagnosis and radioimmunotherapy of cancer.

Animals↗
PubMedDate not supplied

[The interaction of Bradyrhizobium japonicum with clay minerals].

It is shown that such clay minerals as palygorskite and montmorillonite stimulate growth activity of Bradyrhizobium japonicum. The bacteria come into contact with the above minerals. Granulated preparations of rhizobia have been developed on the basis of the results obtained. These preparations are characterized by the high yield of viable cells and a possibility of long-term storage. The use of montmorillonite in production of granulated preparations provides the higher yield of viable bacteria in the preparations and stability of their composition under long-term storage.

Aluminum Silicates↗
PubMed2000

[Somatostatin analogs in the treatment of pancreatic cancer: utopia or feasible alternative?].

The authors give an overview on the clinical treatment results of pancreatic carcinoma with somatostatin analogs including octreotide, lanreotide and vapreotide. Numerous preclinical studies provided solid evidence that the growth of ductal pancreatic adenocarcinoma can successfully be inhibited using such synthetic analogs via direct (apoptosis-inducing) and various indirect mechanisms. In the clinical practice their role still remains contradictory. Monotherapy did not result in a prolongation of the survival, however, in 15-20% of patients the progression of the process has been halted for several months accompanied by a significant improvement of the clinical condition without notable side effects. Combination of octreotide with tamoxifen yielded a survival benefit in addition to the stabilization of the general condition, although reduction of the tumor mass has not been documented. Despite the modest results these finding reinforce the responsiveness of the pancreatic ductal cancer to the hormonal manipulations and further studies on optimization of the effects are of worth. While in the majority of cases the somatostatin receptors have been lost, hormonal control of the pancreatic cancer could be achieved by combination treatment modalities.

Antineoplastic Agents↗
PubMed1979

Equivalence of microbiological and hydroxylamine methods of analysis for ampicillin dosage forms.

Ampicillin formulations were assayed by microbiological and hydroxylamine methods to determine whether thehydroxylamine analytical method is a suitable substitute for the microbiological method. Paired assay results by the 2 analytical methods were obtained on different strengths of tablet, capsule, and suspension, formulations containing ampicillin and ampicillin degradation compounds. Several statistical tests were used to assess the equivalence of the paired assay results. The data analyses indicate that the hydroxylamine method is a suitable substitute for the microbiological method for potency assays and stability studies of ampicillin formulations. The hydroxylamine method yielded slightly higher assay results than the microbiological method for severely degraded formulations.

Ampicillin↗
PubMed2003

Yersinia enterocolitica sepsis in an adolescent with Cooley's anemia.

Human infections due to Yersinia enterocolitica have been reported worldwide, predominantly in Europe. However, there have been few reports of Yersinia enterocolitica infection in Taiwan. We report a case of Y. enterocolitica sepsis in a 15-year-old Taiwanese girl with Cooley's anemia and insulin-dependent diabetes mellitus. She presented at admission with fever, shock and consciousness disturbance. She had symptoms of abdominal pain, vomiting and diarrhea for three days before admission. Blood pressure stabilized after intravenous normal saline rescue. Blood culture yielded Y. enterocolitica 2 days later and ceftriaxone was administered according to the results of sensitivity tests. She recovered well after a course of antibiotic treatment. Though Y. enterocolitica sepsis is rare in Taiwan, clinicians should be aware of its tendency to develop in patients with Cooley's anemia, fever and enterocolitis and that its clinical course may include sepsis leading to shock.

Adolescent↗
PubMed1989

Methane monooxygenase from Methylosinus trichosporium OB3b. Purification and properties of a three-component system with high specific activity from a type II methanotroph.

Methane monooxygenase has been purified from the Type II methanotroph Methylosinus trichosporium OB3b. As observed for methane monooxygenase isolated from Type I methanotrophs, three protein components are required: a 39.7-kDa NADH reductase containing 1 mol each of FAD and a [2Fe-2S] cluster, a 15.8-kDa protein factor termed component B that contains no metals or cofactors, and a 245-kDa hydroxylase which appears to contain an oxo- or hydroxo-bridged binuclear iron cluster. Through the use of stabilizing reagents, the hydroxylase is obtained in high yield and exhibits a specific activity 8-25-fold greater than reported for previous preparations. The component B and reductase exhibit 1.5- and 4-fold greater specific activity, respectively. Quantitation of the hydroxylase oxo-bridged cluster using EPR and Mössbauer spectroscopies reveals that the highest specific activity preparations (approximately 1700 nmol/min/mg) contain approximately 2 clusters/mol. In contrast, hydroxylase preparations exhibiting a wide range of specific activities below 500 nmol/min/mg contain approximately 1 cluster/mol on average. Efficient turnover coupled to NADH oxidation requires all three protein components. However, both alkanes and alkenes are hydroxylated by the chemically reduced hydroxylase under single turnover conditions in the absence of component B and the reductase. Neither of these components catalyzes hydroxylation individually nor do they significantly affect the yield of hydroxylated product from the chemically reduced hydroxylase. Hydroxylase reduced only to the mixed valent [Fe(II).Fe(III)] state is unreactive toward O2 and yields little hydroxylated product on single turnover. This suggests that the catalytically active species is the fully reduced form. The data presented here provide the first evidence based on catalysis that the site of the monooxygenation reaction is located on the hydroxylase. It thus appears likely that the oxo-bridged iron cluster is capable of catalyzing oxygenase reactions without the intervention of other cofactors. This is a novel function for this type of cluster and implies a new mechanism for the generation of highly reactive oxygen capable of insertion into unactivated carbon-hydrogen bonds.

Cell-Free System↗
PubMed1989

[External instrumental fixation of the spine in the treatment of spinal diseases and injuries].

The authors analyze the results of treatment of 358 patients with specific and nonspecific spondylitis and with aftereffects of unstable fractures of the vertebrae proper, who have been operated on the spine destruction or instability area with the extrafocal fixation of the operated on segments by means of the Byzov apparatus. This method has yielded good clinical and functional results, effected the stability of the anterior and posterior portions of the operated on sites; it permits early (starting from the 5th-10th day postoperation) exercise of the patients, helps normal functioning of the body organs and systems, and activates the repair processes in the operated on sites. The incidence rate of the postoperative complications drops drastically, the patients rapidly recover their working abilities, and the invalidism is more rare.

Adolescent↗
PubMed1979

Aminoglycoside antibiotic measurement by bioluminescence, with use of plasmid-coded enzymes.

We describe a bioluminescent assay for gentamicin in serum that is applicable to the measurement of other aminoglycosides as well. The assay is based on the measurement of residual ATP with the luciferase reaction after incubation of the antibiotic with a plasmid-coded enzyme. Two aminoglycoside-inactivating enzymes were used: an adenylytransferase and an acetyltransferase coupled to S-acetyl coenzymeA synthetase. We investigated the latter system further because of the good stability of the acetyltransferase, its recovery in high yield from bacteria, and its more favorable ATP/gentamicin mass ratio. Serum ATPases were inactivated at 60 degrees C for 20 min. The operating range of the assay was 0-15 mg of gentamicin per liter. The precision (CV) was 10.1% at a concentration of 2 mg/L and 1.1% at 10 mg/L. The method correlated well with a radio-enzymatic assay for mock unknown sera (r = 0.981). The results were available within 2 h.

Acetate-CoA Ligase↗
PubMed1982

[Rheological properties of solutions of purified hemoglobin and blood].

The results of studying rheological properties of solutions of purified hemoglobin and its mixtures with blood indicate low relative viscosity of the solutions, as well as an appreciable decrease, when the blood is diluted with these solutions, of the indicators of its viscosity and yield stress without impairment of the blood suspension stability. This allows the conclusion about prospectiveness of further studies aimed at the design of hemocorrectors on the basis of extraerythrocytic hemoglobin.

Blood Sedimentation↗
PubMed1993

TESLA Accelerator Installation at Vinca. Production of radioisotopes for nuclear-medical applications.

The construction of the TESLA Accelerator Installation has been in progress under way at Vinca. It was designed so that the parameters of its main part-the VINCY Cyclotron enable, besides other applications, also the production of a number of radioisotopes which can be used in nuclear medicine. The production of a given radioisotope includes the choice of nuclear reaction (type, energy and beam current of accelerated particles, cross section, yield, etc), target (chemical form, isotopic composition, thermal stability), procedure of chemical treatment of the target after irradiation, procedure of labeling and quality control of the obtained radiopharmaceutical. In the paper these aspects are shown on the example of the production of radioisotope 123I.

Cyclotrons↗
PubMedDate not supplied

[The role of shifts in blood rheology in the genesis of thrombosis in patients with arthrosis deformans of the hip joint].

Blood rheology was studied in 83 patients with deforming coxarthrosis and 32 healthy controls. The following parameters were measured: blood viscosity, hematocrit, yield point, red cell aggregation and deformability, suspension stability. It is shown that blood rheology in coxarthrosis undergoes changes early in the disease course which progress with worsening of the patient's condition. High blood density in coxarthrosis is one of the factors responsible for postoperative thrombotic and thromboembolic complications.

Adolescent↗
PubMed1998

Anterior cervical plate stabilization in one- and two-level degenerative disease: overtreatment or benefit?

This consecutive case retrospective chart review of 356 patients compares the reoperation rate of one- and two-level anterior cervical discectomies for degenerative disease with and without anterior cervical plate stabilization (ACPS). A total of 210 patients underwent surgery without ACPS (bone alone) and 146 patients underwent surgery with the addition of ACPS. Follow-up ranged from 1 to 9 years. A total of 22 patients with one- or two-level cervical arthrodesis required a second surgical intervention (19 bone alone, 3 with ACPS). Reoperations were performed in the bone-alone group for pseudarthrosis in 12 cases and for progression of degenerative disease in 7 cases. The reoperations in the ACPS group were performed for pseudarthrosis in one case and settling of the graft with screw fracture before fusion in two cases. The log-rank test, which uses all patients and their total follow-up periods, was statistically significant in favoring ACPS (p = 0.05). Furthermore, the reoperation rate after 1 year was also significantly lower when ACPS was utilized compared with bone alone (p = 0.0308, Fisher's exact test, two tailed). These data provide evidence that the addition of ACPS in one- and two-level cervical degenerative disease does not constitute overtreatment but rather supplements the internal stabilization initially provided by the bone graft and yields a lower reoperation rate.

Adult↗
PubMed2006

A Rorschach stability study in a nonpatient adult sample.

The objective of this study was to provide new primary data on Rorschach Comprehensive System stability levels. To achieve this, we tested 75 French nonpatient adults twice on the Rorschach with a 3-month interval between the tests. Interrater reliability was in the excellent range for most of the variables studied. The overall stability level in a selected set of previously studied variables was below expectations (median r = .53). Personality, cognitive or self/relational variables yielded higher test-retest correlations than emotional and coping variables. Moderators of stability could be identified: (a) overall level of Task Engagement (TE) in F, m, FM + m, a, FC, Sum C', Sum V, Sum Shd, Fr + rF, INC + FAB, COP, es, Adj es, EGO, and Blends; (b) variations in TE in F, FM, and p; (c) state distress in Zd, m, FM + m, a, C, CF + C, WSumC, FD, and es; (d) variables derived from the number of responses impacted stability in P, Zf, m, FC, CF + C, Sum C', Sum V, MOR, EA, es, and Blends. These results provide further support for the reliability of several measures. Examiner effects as an influence on productivity and TE were identified as an important area for future research.

Adult↗
PubMed1999

Chameleon Thermal Behavior of Cycloadducts of Nitrones to Methyl 2-Chloro-2-cyclopropylidene- and 2-Chloro-2-spiropentylideneacetates.

Methyl 2-chloro-2-cyclopropylideneacetate (2) and its spiropentane analogue 3 cycloadd to dihydroisoquinoline N-oxide (9), pyrroline N-oxide (12), and C-phenyl-N-methylnitrone (16) to give 5-spirocyclopropaneisoxazolidines in good yields (58-93%). The thermal behavior of the 5-spirocyclopropaneisoxazolidines is rather differentiated, depending strongly on the constitution of the nitrone and the solvent. As nitrone 9 has the tendency to undergo cycloreversion reactions, the ketoamide rearrangement products 20 and 21 from its cycloadduct derive from the thermodynamically favored 4-spirocyclopropaneisoxazolidine regioisomers formed after the cycloreversion process. In DMSO as solvent different rearrangement processes take place, leading to benzoindolizinones in modest yields (15-21%). The cycloadducts from 12 and 16 undergo a cyclopropyl to cyclobutyl ring enlargement facilitated by the presence of a chlorine substituent on the carbon alpha to the spirocyclopropane ring. Whereas these compounds from nitrone 16 demonstrated an unusual stability, those from nitrone 12 undergo a cascade rearrangement to yield indolizinone derivatives 34, 35 cleanly (73-83% yield). This overall transformation offers a new method for the synthesis of the indolizine skeleton.

Journal Article↗
PubMed2005

Effects of substituents on the stability of phosphoranyl radicals.

The effect of substituents on the geometries, apicophilicities, radical stabilization energies, and bond dissociation energies of (*)P(CH(3))(3)X (X = CH(3), SCH(3), OCH(3), OH, CN, CF(3), Ph) were studied via high-level ab initio molecular orbital calculations. Two alternative definitions for the radical stabilization energy (RSE) were considered: the standard RSE, in which radical stability is measured relative to H-P(CH(3))(3)X, and a new definition, the alpha-RSE, which measures stability relative to P(CH(3))(2)X. We show that these alternative definitions yield almost diametrically opposed trends; we argue that alpha-RSE provides a reasonable qualitative measure of relative radical stability, while the standard RSE qualitatively reflects the relative strength of the P-H bonds in the corresponding H-P(CH(3))(3)X phosphines. The (*)P(CH(3))(3)X radicals assume a trigonal-bipyramidal structure, with the X-group occupying an axial position, and the unpaired electron distributed between a 3p(sigma)-type orbital (that occupies the position of the "fifth ligand"), and the sigma orbitals of the axial bonds. Consistent with this picture, the radical is stabilized by resonance (along the axial bonds) with configurations such as X(-) P(*+)(CH(3))(3) and X(*) P(CH(3))(3). As a result, substituents that are strong sigma-acceptors (such as F, OH, or OCH(3)) or have weak P-X bonds (such as SCH(3)) stabilize these configurations, resulting in the largest apicophilicities and alpha-RSEs. Unsaturated pi-acceptor substituents (such as phenyl or CN) are weakly stabilizing and interact with the 3p(sigma)-type orbital via a through-space effect. As part of this work, we challenge the notion that phosphorus-centered radicals are more stable than carbon-centered radicals.

Free Radicals↗