Neuroprotective effects of NMDA receptor glycine recognition site antagonism: dependence on glycine concentration

High-affinity NMDA receptor glycine recognition site antagonists protect brain tissue from ischemic damage. The neuroprotective effect of 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021), a selective NMDA receptor antagonist with nanomolar affinity for the glycine binding site, was examined in rat cortical mixed neuronal/glial cultures. ACEA 1021 alone did not alter spontaneous lactate dehydrogenase (LDH) release. Treatment with ACEA 1021 (0.1-10 microM) before 500 microM glutamate, 30 microM NMDA, or 300 microM kainate exposure was found to reduce LDH release in a concentration-dependent fashion. These effects were altered by adding glycine to the medium. Glycine (1 mM) partially reversed the effect of ACEA 1021 on kainate cytotoxicity. Glycine (100 microM-1 mM) completely blocked the effects of ACEA 1021 on glutamate and NMDA cytotoxicity. The glycine concentration that produced a half-maximal potentiation of excitotoxin-induced LDH release in the presence of 1.0 microM ACEA 1021 was similar for glutamate and NMDA (18 +/- 3 and 29 +/- 9 microM, respectively). ACEA 1021 also reduced kainate toxicity in cultures treated with MK-801. The effects of glycine and ACEA 1021 on glutamate-induced LDH release were consistent with a model of simple competitive interaction for the strychnine-insensitive NMDA receptor glycine recognition site, although nonspecific effects at the kainate receptor may be of lesser importance.     

pH-induced conformational changes of membrane-bound influenza hemagglutinin and its effect on target lipid bilayers

Influenza virus hemagglutinin (HA) has served as a paradigm for both pH-dependent and -independent viral membrane fusion. Although large conformational changes were observed by X-ray crystallography when soluble fragments of HA were subjected to fusion-pH conditions, it is not clear whether the same changes occur in membrane-bound HA, what the spatial relationship is between the conformationally changed HA and the target and viral membranes, and in what way HA perturbs the target membrane at low pH. We have taken a spectroscopic approach using an array of recently developed FTIR techniques to address these questions. Difference attenuated total reflection FTIR spectroscopy was employed to reveal reversible and irreversible components of the pH-induced conformational change of the membrane-bound bromelain fragment of HA, BHA. Additional proteolytic fragments of BHA were produced which permitted a tentative assignment of the observed changes to the HA1 and HA2 subunits, respectively. The membrane-bound HA1 subunit undergoes a reversible conformational change, which most likely involves the loss of a small proportion of beta-sheet at low pH. BHA was found to undergo a partially reversible tilting motion relative to the target membrane upon exposure to pH 5, indicating a previously undescribed hinge near the anchoring point to the target membrane. Time-resolved amide H/D exchange experiments revealed a more dynamic (tertiary) structure of membrane-bound BHA and its HA2, but not its HA1, subunit. Finally BHA and, to a lesser degree, HA1 perturbed the lipid bilayer of the target membrane at the interface, as assessed by spectral changes of the lipid ester carbonyl groups. These results are discussed in the context of a complementary study of HA that was bound to viral membranes through its transmembrane peptide (Gray C, Tamm LK, 1997, Protein Sci 6:1993-2006). A distinctive role for the HA1 subunit in the conformational change of HA becomes apparent from these combined studies.     

An ecological study of the effectiveness of mammography in reducing breast cancer mortality

OBJECTIVES: The purpose of this study was to determine the relation of screening mammography to breast cancer incidence and case fatality. METHODS: In a sample of White female Medicare beneficiaries hospitalized in 1990-1991, age-adjusted breast cancer incidence and 2-year case fatality rates were estimated and compared with the frequency of mammographic screening from a population-based survey. RESULTS: The average rates for incidence, case fatality, and mammography within 5 years in 29 states were 414/100,000, 18.8%, and 59.2%, respectively. There was a positive state-level correlation between mammography rates and incidence and an inverse correlation between mammography and case fatality. CONCLUSIONS: High screening mammography rates in some states are associated with reduced breast cancer case fatality rates, presumably as a result of diagnosis of earlier stage cancers.     

Effects of dietary boron supplementation on broilers

Two experiments were conducted with a total of 432 broiler chicks to investigate the influence of supplementing different amounts of boron to practical corn-soybean meal diets. The birds were housed in batteries and had free access to feed and water. In Experiment 1, 144 1-day-old broiler chicks were fed a basal diet supplemented with 0, 5, 40, 80, or 120 ppm boron for 21 days. Female body weight was not influenced by the dietary treatments. However, males supplemented with 5 ppm boron were heavier and their tibias resisted more load than the control birds. Overall feed conversion was not influenced by boron. In Experiment 2, 288 1-day-old broiler chicks were fed a basal diet supplemented with 0, 60, 120, 240, or 300 ppm boron for 22 days. Male and female body weights of the 300-ppm group were lower than those of the control birds. Percentage tibia ash was highest with 300 ppm boron. No significant differences were found in intestinal tract weight (grams of intestine per 100 g body weight) among treatments. Boron concentration in the breast muscle and liver increased as dietary concentration of boron increased. Data collected in these two experiments indicated that consumption of diets containing up to 240 ppm boron from hatch to 21 days of age was not detrimental to broiler performance. Data were not conclusive on the need for supplemental boron in broiler diets based on corn and soybean meal.     

A study of the competitive nitrosations of pyrrolidine,ascorbic acid,cysteine and p-cresol in a protein-based model system

The effects of competitive C- and S-nitrosations on the formation of nitrosopyrrolidine were studied in a protein-based model system. The results obtained were compared with those of the analogous reactions performed in solution. The competitive nitrosations were studied at pH 5-25 and 37°C and the results obtained were found to be similar in both systems: ascorbic acid, cysteine and p-cresol each reduced the formation of nitrosopyrrolidine, in decreasing amounts, by competing with pyrrolidine for the available nitrite. A second pathway of nitrosopyrrolidine formation was found which may have involved transnitrosation by the protein-bound nitrite.     

A high repetition rate ion laser spanning the 195-225 nm spectral region

This paper describes the construction and operation of a water-cooled noble gas ion laser which generates average powers of the order of a milliwatt at 5 strong transitions between 195 and 225 nm. This pulsed laser has been operated at repetition rates up to 200 Hz and has produced average powers up to 5.1 mW at 219.2 nm. The pressure and voltage dependence of output power, along with preionization effects, gain, saturation intensities, and the effects of discharge current pulse length are discussed. The optical pulses can be precisely synchronized with respect to an electrical reference signal, and the laser operates at all wavelengths with Brewster windows, permitting convenient interchanging of resonator mirrors. This device has been designed for use as an ultraviolet illuminator in a photoelectron microscope.     

The effect of the long-term alcoholization of rats on partial kidney functions under increasing hypo- and hyperosmolarity

After prolonged alcoholisation of rats the water loads paradoxically induced a lesser water and univalent cations excretion as compared with the control. The same animals excreted less water and sodium and more potassium after the salt loads.     

Gain limitations in optical parametric amplifiers

Factors limiting the gain of parametric amplifiers pumped by the 266 nm harmonic of aQ-switched Nd:YAG laser have been investigated, and the advantages of combined parametric/dye amplifiers in the visible are discussed.     

Swing-lock design considerations for obturator frameworks

The conventional and swing-lock (S/L) obturator prostheses can be highly effective in restoring maxillary defects when careful attention is paid to the principles of framework design. Although the S/L modality has been available since the mid 1960s, its use in maxillofacial prosthetics has been limited, and little information is available in the literature to guide the practitioner. This modality offers a conservative design option that lies somewhere between the conventionally designed obturator prosthesis and the prosthesis designed to use extensive fixed reconstruction or endosseous implants. When the S/L obturator is considered, single, double, or dual labial bar designs are possible and may be required by the length and complexities of the arc of closure. Such designs provide a flexible labial bar that transmits less stress to abutment teeth. This article reviewed conventional obturator framework designs and compared them with S/L designs for similar patient categories.