Direct absorption spectroscopy of water clusters formed in a continuous slit nozzle expansion.

In this article, we report on a Fourier transform infrared study of absorption bands belonging to small-sized water clusters formed in a continuous slit nozzle expansion of water vapor seeded in argon carrier gas. Clear signatures of free and H-bonded OH vibrations in water aggregates from dimer to pentamer are seen in our spectra. Following an increase in argon backing pressure, the position of the cluster absorption bands varies from those characteristics of isolated water aggregates in the gas phase to those known for clusters trapped in a static argon matrix. These variations can be interpreted in terms of sequential solvation of the water clusters by an increasing number of argon atoms attached to water clusters. Our measured spectra are in good agreement with those obtained previously either for free or Ar coated small-sized water clusters using pulsed slit-jet expansions. Our results are equally in accord with those originating from a variety of tunable laser based techniques using molecular beams or free jets or from the study of water aggregates embedded in rare gas matrices. Distinctions are reported, however, and discussed. Ab initio calculations have made it possible to speculate on the average size of an argon solvation shell around individual clusters as well as on the development of the OH stretch vibrational shifts in mixed (H(2)O)(m)Ar(n) clusters having different compositions and architectures.

Evaluation of the diagnostic value of the first thyroglobulin determination in detecting metastases after differentiated thyroid carcinoma surgery.

AIM: Evaluation of the diagnostic value of the first thyroglobulin (Tg) level measurement, performed after thyroidectomy, before another treatment, as an early marker of either metastases or local recurrence of differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: Data of 178 patients (160 women, 18 men, 14-79 years) with DTC and without known interference in Tg assay were evaluated retrospectively. In all patients, neck radioiodine uptake (Tup (24)), thyroid remnants volume (V), TSH and Tg were measured. The Tg/V and Tg/Tup (24) ratios were calculated to correct Tg concentration with regard to V and Tup (24). Six months after initial evaluation and routine therapy all patients underwent control examinations under endogenous TSH stimulation. RESULTS: During follow-up metastases or local recurrence were found in 32 patients. The groups of patients with no diagnosed metastases (M0) and with detected metastases (M1), did not differ with regard to V, serum TSH or Tup (24); difference between the two groups was found in Tg concentration (4.3 ng/ml VS 97.4 ng/ml; p=0.000001). The ratios of Tg/Tup (24) (p=0.000000) and Tg/V (p=0.004) were lower in the group M0 than M1. The areas under receiver operating characteristic curves (ROC) for Tg concentrations, Tg/Tup (24), and Tg/V ratios were 0.773 (95% CI - 0.655-0.892), 0.817 (0.709-0.925) and 0.712 (0.541-0.884), respectively. CONCLUSIONS: Both the absolute Tg concentration and Tg/V and Tg/Tup (24) ratios, determined after thyroidectomy but before another treatment in patients with metastases of DTC, diagnosed within 6 months after (131)I administration, are higher than those in patients without such metastases. This indicates that the mentioned parameters may be applied as early markers of either local recurrence or metastases of DTC. The highest discriminative value demonstrates Tg/Tup (24) ratio, Tg concentration has a lower value and Tg/V ratio has the lowest one.

The effect of molecular weight on nonspecific accumulation of (99m)T-labeled proteins in inflammatory foci.

UNLABELLED: Although several proteins have been proposed and tested for scintigraphic detection of infection, the most optimal characteristics of a protein for this application have not yet been determined. Molecular weight (MW) of the protein, its charge, shape, carbohydrate content, characteristics of the radionuclide and receptor interactions are factors that could affect the in vivo behavior of the infection imaging agent. The effect of molecular weight on nonspecific accumulation of (99m)Tc-labeled proteins in inflammatory foci was studied in a rat model. METHODS: Eleven proteins whose MWs ranged from 2.5 kDa up to 800 kDa were labeled with (99m)Tc using the hydrazinonicotinamide (HYNIC) chelator. Rats with S. aureus infection were injected i.v. with 15 MBq (99m)Tc-labeled protein. Gamma camera images were acquired and biodistribution of the radiolabel was determined ex vivo. RESULTS: From biodistribution data no significant correlation was found between abscess uptake and molecular size of the (99m)Tc-labeled proteins that were studied. Fast blood clearance with predominant uptake in liver and spleen was found for the largest proteins (MW 669 kDa-800 kDA). For proteins of intermediate size (MW 66 kDa -206 kDa) we found relatively slow blood clearance with relatively moderate uptake in liver and spleen. For smaller proteins (MW 2.5 kDa -29 kDa) rapid blood clearance with predominant kidney uptake was observed. The abscess uptake of the (99m)Tc-labeled proteins (%ID/g, 24 h p.i.) was highest for serum proteins IgG and BSA. Abscess uptake correlated well with blood levels: r = 0.95 and 0.84 at 4 and 24 h respectively (P < 0.005). The abscess-to-muscle ratios varied from 2.1 to 17.8 at 24 h p.i. with highest values for alpha-2 macroglobulin (MW 725 kDa) and the intermediate sized proteins (MW 66-206 kDa). Gamma camera imaging showed localization of all radiotracers at the site of infection with abscess-to-background ratios (A/B) ranging from 1.4 to 7.0 (IgG) at 20 h p.i. The serum proteins IgG and BSA showed highest blood levels and best infection imaging characteristics. CONCLUSION: Not molecular weight but blood residence time is the principal factor that determines localization of a nonspecific tracer protein in infectious foci. The ideal nonspecific infection imaging agent is a protein with a long circulatory half-life. From the proteins tested here IgG and albumin showed the best characteristics for an infection imaging agent.

Transformation by Hras(G12V) is consistently associated with mutant allele copy gains and is reversed by farnesyl transferase inhibition.

RAS-driven malignancies remain a major therapeutic challenge. The two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) model of mouse skin carcinogenesis has been used to study mechanisms of epithelial tumor development by oncogenic Hras. We used mice with an Hras(G12V) knock-in allele to elucidate the early events after Hras activation, and to evaluate the therapeutic effectiveness of farnesyltransferase inhibition (FTI). Treatment of Caggs-Cre/FR-Hras(G12V) mice with TPA alone was sufficient to trigger papilloma development with a shorter latency and an ∼10-fold greater tumor burden than DMBA/TPA-treated WT-controls. Hras(G12V) allele copy number was increased in all papillomas induced by TPA. DMBA/TPA treatment of Hras(G12V) knock-in mice induced an even greater incidence of papillomas, which either harbored Hras(G12V) amplification or developed an Hras(Q61L) mutation in the second allele. Laser-capture microdissection of normal skin, hyperplastic skin and papillomas showed that amplification occurred only at the papilloma stage. HRAS-mutant allelic imbalance was also observed in human cancer cell lines, consistent with a requirement for augmented oncogenic HRAS signaling for tumor development. The FTI SCH66336 blocks HRAS farnesylation and delocalizes it from the plasma membrane. NRAS and KRAS are not affected as they are alternatively prenylated. When tested in lines harboring HRAS, NRAS or KRAS mutations, SCH66336 delocalized, inhibited signaling and preferentially inhibited growth only of HRAS-mutant lines. Treatment with SCH66336 also induced near-complete regression of papillomas of TPA-treated Hras(G12V) knock-in mice. These data suggest that farnesyl transferase inhibitors should be reevaluated as targeted agents for human HRAS-driven cancers, such as those of bladder, thyroid and other epithelial lineages.

Wildlife identified as major source of Escherichia coli in agriculturally dominated watersheds by BOX A1R-derived genetic fingerprints.

The presence of Escherichia coli in recreational and potable waters is a major concern to the general public as elevated levels of E. coli suggest the presence of pathogenic bacteria and viruses. Unfortunately, traditional microbial techniques do not allow specific identification of the source of E. coli. This reduces the ability to target management practices that reduce bacterial contamination. In the Finger Lakes region of western New York, USA, wildlife resides in relatively high densities on watersheds dominated by people and dairy farms, and as a result, the sources of fecal degradation of potable and recreational waters are often unknown. In the Conesus Lake watershed, the sources of microbial contamination were assessed using Rep-PCR molecular tools, a method of amplifying repetitive DNA sequences found throughout the E. coli genome to produce distinct fingerprints for a given ecotype. Molecular fingerprints of E. coli isolated from regional populations of cattle, humans, geese and deer were compared to E. coli isolated from stream water samples. Canonical discriminant function analysis indicated that the DNA fingerprints of the original source group isolates were correctly predicted 90.2% of the time. Since land use in the sub-watersheds was dominated by dairy and cash crop farms, it was expected that the majority of E. coli isolated would be identified as cows; however, an unexpectedly high percentage of isolates were identified as wildlife (geese and deer). Geese were the dominant source of E. coli (44.7-73.7% of the total sources) in four sub-watersheds followed by cows (10.5-21.1%), deer (10.5-18.4%), humans (5.3-12.9%) and unidentifiable sources (0.0-11.8%). Management practices intended to decrease the number of cattle or the amount of manure spread in a sub-watershed were reflected in a decrease of E. coli ecotypes associated with dairy cows.

The Inversion-Torsion Potential Function for Hydrazine

The torsion-inversion potential surface for hydrazine has been determined from the rovibrational data using a new rotation-torsion-inversion Hamiltonian. All elements of the inverse moment of inertia tensor have been expanded into mixed Fourier series of large amplitude coordinates. That gives two major advantages: (i) no numerical integration is necessary at any step of calculation, and (ii) the three-dimensional integrals have been replaced by the products of one-dimensional integrals. It has been proven that the inversion-torsion coupling in hydrazine is negligible and the inversion-inversion coupling is very strong. The barrier to inversion of 2072 cm-1 is slightly higher than that in ammonia and the barrier to internal rotation of 934 cm-1 is relatively high but lower than that determined previously from one-dimensional models.

Ab Initio Potential Energy Surface and Internal Torsional-Wagging States of Hydroxylamine

The two-dimensional potential energy surface describing the interaction of the large-amplitude torsional and wagging motions in hydroxylamine has been determined from ab initio calculations. This surface has been sampled by a large set of grid points from a two-dimensional configuration space spanned by the torsional and wagging coordinates. At each grid point, the geometry optimization has been performed using the second-order Moller-Plesset perturbation theory with the basis set 6-311 + G(2d, p). At the optimized geometry, the single-point calculation of the electronic energy has been carried out using a larger basis set 6-311 + G(3df, 2p). This method was verified to yield the results comparable to those obtained by a direct optimization of the geometry with the basis set 6-311 + G(3df, 2p) which had been used by A. Chung-Phillips and K. A. Jebber (1995. J. Chem. Phys. 102, 7080-7087) to calculate the energies of only three points in the potential energy surface of hydroxylamine. The trans and cis local minima have been found on the determined potential energy surface. The localization features of the torsional-wagging states have been studied by solving the two-dimensional Schrodinger equation for the coupled torsional and wagging motions. Copyright 1997 Academic Press. Copyright 1997Academic Press

Iodine-induced hyperthyroidism--an epidemiological survey several years after institution of iodine prophylaxis in Poland.

In 1997, the obligatory model of iodine prophylaxis was introduced in Poland in order to correct the existing status of mild and/or moderate iodine deficiency. In order to monitor possible side-effects of increased iodine supply, studies on iodine-induced hyperthyroidism were initiated by establishing several regional registers of hyperthyroidism. In the present paper, the results of a two-year monitoring (2000-2001) have been summarized. There are no epidemiological data on hyperthyroidism prior to starting the iodine prophylaxis, but the obtained current data are comparable to observations in other countries, made after iodine supplementation. The incidence of iodine-induced hyperthyroidism did not exceed the acceptable level, thus confirming--together with previous observations on the effectiveness of iodine prophylaxis--the adequacy of applied dose of KI (30 microg/kg NaCl), used for salt iodization in Poland.