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2-(4-Pyridyl)-5-phenyloxazole (4PyPO) and its pyridinium salts have been investigated for laser action in the violet and blue-green spectral regions, respectively. The phenyloxazolyl pyridinium salts show good lasing characteristics, broad tuning ranges, and superior photochemical stability when compared with coumarin 175 in water. Recommendations were made on how the lasing maxima could be blue or red shifted and how the output power and photochemical stability of the new classes of laser dyes could be made to approach that of C8F, which is one of the most photochemically stable lasing dyes reported to date. Because of the reactivity of the nonbonding electrons on the pyridyl group of 4PyPO, hundreds of new laser dyes are possible from the parent dye. A new generation of water soluble, low threshold multifluorophoric laser dyes capable of intramolecular energy transfer and intramolecular triplet state quenching was proposed.

Interleukin 4 (IL 4), formerly known as B cell stimulatory factor 1 (BSF-1), has recently been described as a growth factor for T cells. The role of IL 4 in the putatively IL 2-independent growth of certain cloned T helper cells is unclear. D10.G4.1 (D10) is a conalbumin-specific helper T cell that has been employed extensively in the analysis of T cell activation and as an assay for the detection of IL 1. Previously, it was thought that IL 1 induced the expression of IL 2 receptors on D10 cells, thereby permitting D10 to proliferate in response to endogenously produced IL 2. However, we cannot detect IL 2 mRNA or protein in D10 cells or their supernatants as determined by the following criteria: monoclonal antibodies that neutralize the in vitro activity of murine IL 2 do not block the IL 1-dependent proliferation of D10 cells; no competitive binding for high-affinity IL 2 receptors with 125I-labeled IL 2 can be detected with medium conditioned by activated D10 cells; and Northern blot analysis and S1 nuclease protection assays, performed with cDNA probes for IL 2, do not detect mRNA for IL 2 under a variety of different activation conditions that foster autocrine growth of D10 cells. In contrast, activated D10 cells produce both IL 4 mRNA and protein as judged by similar criteria. Purified IL 4 has significant TCGF activity as measured by proliferation of HT-2 cells. This activity can be blocked completely by a monoclonal antibody to IL 4 (11B11). The proliferation of D10 cells in the presence of 3D3 (a clonotype-specific monoclonal anti-T cell receptor antibody) and IL 1 can be blocked completely by 11B11 antibody. Highly purified IL 4 alone cannot induce the proliferation of resting D10 cells; however, equivalent amounts of IL 4 in the presence of recombinant IL 1 induce significant D10 proliferation. Therefore, IL 1 appears to render D10 cells responsive to their autocrine growth signal. These data indicate that IL 4 serves as the autocrine T cell growth factor for D10 cells, and that exogenous IL 1 is required for the transduction of this growth signal. This may represent a more broadly applicable mechanism for the growth of certain subsets of T helper cells.

The effect of gamma radiation on the screw-worm fly, Chrysomya bezziana, was studied to determine the optimum dose and stage for sterilisation. Laboratory cultured flies were exposed in a gamma irradiator with a cesium-137 source. Treated flies were compared with untreated controls for adult emergence, survival, insemination and fertility. Puparia treated with 5 krad at 1–2 d before emergence were rendered infertile but not otherwise adversely affected. When flies were irradiated early in pupal development, adverse effects were apparent. When late puparia were irradiated with 1–8 krad, adult emergence, survival and rate of insemination were similar to controls. Complete sterility of males and females was achieved with 4 krad. There was no larval survival from eggs when both parents were treated with 1 or more krad but larval survival was recorded from eggs laid by untreated females mated with 1–2.5 krad treated males and from eggs laid by 1–1.5 krad treated females mated with untreated males. There was no recovery of fertility after sterilisation with 4 krad. Irradiation of males at 2–6 krad as late puparia did not impair mating competitiveness in laboratory tests. In a field evaluation of male competitiveness, the release of sterile males at a density of 144 males per km2 per week over a 78 km2 area for 7 weeks resulted in 25 per cent sterility in the native screw-worm fly population after 4 weeks of releases.

In tests involving 270 calves treated orally with single doses of systemic insecticides in bolus form, Dow ET-57 (Trolene) and Dowco-109 (phosphoramidothioic acid, methyl 1-, O -(-4- tert - butyl-2-chlorophenyl) O -methyl ester), gave high kills of Hypoderma lineatum (DeVill.) and H. bovis (L.). Control with both insecticides exceeded 90%. Dow ET-57 appeared to be as effective at a dosage rate of 85 mg./kg. as at 110 mg./kg. Dimethoate ( O,O ,-dimethyl-S- (N-methylcarbamolymethyl) phosphorodithioate), also called Am. Cyanamid 12,880, gave only erratic control at rates of 15 and 10 mg./kg. None of the three insecticides, when given orally, killed 100% of cattle lice, but dimethoate produced higher kills than Dow ET-57 or Dowco-109. When given as feed additives to 160 calves, Dowco-109 at 2.0, 7.5, and 15 mg./kg. fed for 10,2, and 1 day, respectively, and Dow ET-57 at 55 mg./kg. fed for 2 days, caused grub reductions of 61 to 82%. Better results might have been obtained under more normal feeding conditions than prevailed in this test. As a complete coverage spray, Bayer 21/199 (Co-ral) 0.25 and 0.5% (from wettable powder) provided excellent louse control for at least 5 months. Dowco-109 (wettable powder) provided good louse control for a period of from 3 to more than 4 months. Neither Bayer 21/199 nor Dowco-109 gave satisfactory control of grubs under the conditions of these spray tests, although each gave about 80% control in one test at a concentration of 0.5%. It was concluded that Bayer 21/199 might potentially provide “one-shot” grub and lie control on cattle.

Patient education and involvement is a vital part of quality medical care in chronic diseases, such as diabetes mellitus. In this study the acceptance and effectiveness of programmed machine instruction was evaluated. Young diabetics and their parents can be taught about the disease and its control using an automated technic. There was no objective evidence to indicate control of the disease was significantly improved over a brief period of three months. Patients and parents participating in this study expressed acceptance of programmed instruction as a valuable adjunct to the total education process but stated that this technic should not be the sole educational method employed.

The results show that the rearing temperature for Musca domestica larvae affects the sphingosine composition of ceramide phosphorylethanolamine and the fatty acid composition of phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine. When the rearing temperature was increased from 24 to 29°C. and to 37°C., the amount of hexadecasphinganine and hexadecasphing-4-enine increased and the amount of tetradecasphing-4-enine decreased. Similarly, as the rearing temperature was increased, the ratio of unsaturated to saturated fatty acids isolated from phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine decreased. The temperature-dependent changes in fatty acid composition were greatest for phosphatidylcholine, and were different for each of the above-mentioned phospholipids. The greatest changes were in C 16:1 . Rearing the larvae in an atmosphere of pure oxygen did not affect the fatty acid composition.

Objectives : this study examined the effect of immune modulation therapy (IMT) on claudication distances Materials and methods : a double-blind placebo controlled trial was performed on patients with disabling intermittent claudication with randomisation stratified for short and long distance IC. For IMT, following exposure to UV light, oxidisation and 42.5°C, 10 ml of citrated autologous blood was administered by intra-muscular injection. One course consisted of 6 injections in 3-weeks followed by 3-weeks rest. Patients received 2, 3 or 4 courses depending on response. The primary end-point was the number of responders (>50% increase in initial claudication distance (ICD)) in each group. Secondary end-points included percentage changes in ICD and change in quality of life. Results : at week 24, there were more responders in the IMT group (20/31, 65%) compared to placebo (16/39, 41%) ( p =0.06). In the subgroup of short distance claudicants this difference reached significance (IMT 17/26, 65%) (Placebo12/33, 36%) ( p =0.04). The median increase in ICD was significantly greater in the IMT group (81%) compared to placebo (44%, p =0.04). These results were supported by quality of life measurements. Conclusions : IMT is a safe and apparently effective treatment for patients with short distance claudication.

The response of rabbit tongue, placed in a modified Ussing chamber, to salts [KCl, NaCl, NH4Cl, tetraethylammonium chloride (TEACl)], sweeteners (D-glucose, sucrose), acid (HCl), and a bitter tastant, quinine, was investigated for the first time. These experiments were conducted to further explore the new paradigm of taste transduction that correlates changes in the electrical behavior of lingual epithelia with neural responses. In addition, the responses of rabbit tongue data were compared with previously published data on dog and frog tongues. When increases in short-circuit current (Isc) for rabbit tongue induced by hyperosmotic concentrations of several salts were compared, the following sequence was found: KCl greater than NH4Cl greater than NaCl greater than TEACl. These results are consistent with previously published integrated chorda tympani responses (ICTR) as well as behavioral studies that showed that rabbits prefer KCl to NaCl with their natural diet. Pharmacological studies using ouabain and amiloride suggest that K and Na are traversing rabbit tongue through different pathways. The maximal stimulation of Isc by D-glucose and sucrose (in 50 mM NaCl) was significantly smaller than those measured for KCl and NaCl. The rabbit tongue was sensitive to HCl at concentrations less than 1 mM in agreement with ICTR measurements.

This report describes the accidental poisoning of over 200 head of Holstein cattle by the organophosphate, terbufos. The ingestion of an acutely toxic dose (approximately 7.5 mg/kg) of terbufos by 84 heifers resulted in severe respiratory distress as the primary clinical sign and death within 12 hours. There was no response to treatment with atropine sulfate. One hundred and twenty milking cows received a portion of the contaminated feed diluted approximately ten times. These cattle had typical signs of organophosphate poisoning and responded to atropine sulfate. Severely affected cows received pralidoxime chloride and activated carbon 48 h after terbufos ingestion but did not respond to the drugs. Diagnosis of organophosphate poisoning was confirmed by tissue and feed analysis for terbufos and measurement of whole blood cholinesterase activity.

Twenty-four insulin-dependent diabetic patients were interviewed immediately after a follow-up visit to an outpatient pediatric clinic to determine which of the recorded instructions delivered by professionals were recalled by patients. The health care team reported giving an average of seven recommendations per patient, or a total of 168 items listed by team members as important. Patients recalled an average of two recommendations, or a total of 50 items, 40% of which had not been recorded by team members. Recommendations concerning diet, insulin dosage and injections, urine testing, and exercise represented 80% of those recalled by patients and only 58% of those recorded by professionals. The results were interpreted to suggest that health care teams focus on fewer items to insure communication of the most appropriate recommendations for individual patients.

Responses of isolated canine lingual epithelium in an Ussing chamber to D-glucose and fructose reveal events associated with taste transduction. With the use of isotopic flux studies, together with ion substitution and pharmacological and voltage clamp measurements, it was found that the stimulation of ion transport by D-glucose arises from an increase in the influx of cations through a cation-selective pathway. This influx of cations is completely inhibited by 0.1 mM amiloride. The stimulation of transport by fructose in 0.05 M KCl and by D-glucose in 0.05 M RbCl was also inhibited by amiloride, demonstrating that the saccharide-stimulated entry pathway was specific for neither hexose sugars nor for Na. Saccharide stimulation of canine lingual epithelia does not appear to be modulated by increases in intracellular levels of adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic monophosphate, or Ca. The Na that enters taste cells on saccharide stimulation exits them via the ouabain inhibitable Na+-K+-adenosinetriphosphatase located in the serosal membranes.

Front and rear regions of dog tongue were tested for spatial heterogeneity with respect to monovalent chloride salts (NaCl, KCl, and NH4Cl) and sweet tastants (sucrose, D-glucose, and L-glucose) by placing them in Ussing chambers where the open-circuit potential, Voc, and short-circuit current, Isc, were measured. The responses of Voc and Isc to 0.5 M NaCl were greater in the front of the tongue than in the rear, whereas the responses of Voc and Isc to 0.5 M sucrose were greater in the rear of the tongue than in the front. These results are similar to those of published neurophysiological measurements from the chorda tympani nerve and thalamus. These data suggest that the spatial heterogeneities seen in higher taste centers are present in the isolated lingual epithelium where primary taste transduction events occur.

Hypokinetic/hypodynamic and antiorthostatic responses to weightlessness and bedrest were simulated in mice using a suspension technique. Animals were suspended for 1 or 2 weeks in an antiorthostatic posture and positioned to permit freedom of movement but eliminate load bearing by the hindlimbs. Suspended mice exhibited reduced food and water intakes and rapid 10% decrease in body weight to a level which was maintained for the remainder of the suspension period. Diuresis was evident in suspended mice, but the natriuresis and kaliuresis previously observed in the suspended rat were not evident. Differential hindlimb muscle atrophy (soleus greater than plantaris = gastrocnemius greater than EDL) and increased excretion of urea and ammonia were also noted in suspended mice. Postsuspension recovery studies indicated that the recovery process was highly effective. These results document specific responses to hypokinesia/hypodynamia and antiorthostasis in the mouse and demonstrate similarities in the responses of mice and rats to suspension. These studies expand the utility of the suspension model and suggest that the mouse may be useful in future studies simulating both weightlessness and bedrest.

Background Experimental studies have shown that endothelial dysfunction is an early event preceding restenosis. Monocytes and neutrophils have been shown to bind to damaged endothelium via the cell adhesion molecules (CAMs). The selectins are involved in capturing the leukocytes and tethering them to the endothelium. E-selectin is a CAM that is only expressed on activated endothelial cells. Its ligands are expressed on monocytes and neutrophils and it has been found to exist in a soluble form. This soluble form may represent a marker for endothelial damage and may be a precursor of smooth muscle proliferation. Methods and Results Fifty-four patients who were undergoing peripheral arterial balloon angioplasty had blood sampled before angioplasty. E-selectin was measured in plasma with the use of an ELISA. At follow-up angiogram, 30% (n=14) of the patients had restenosed at 1 year. There was a significant difference in baseline E-selectin levels in patients who restenosed compared with those who did not (65.3 ng/mL [58.25 to 78.05] versus 52.3 [34.2 to 62.1], Mann-Whitney U , P Conclusions We have shown an increased level of shed E-selectin in patients destined for restenosis and suggest that this work further supports a role for white blood cell/endothelial interaction in restenosis after angioplasty.

The first large scale analysis of in vitro absorption, distribution, metabolism, excretion, and toxicity (ADMET) data shared across multiple major pharma has been performed. Using advanced matched molecular pair analysis (MMPA), we combined data from three pharmaceutical companies and generated ADMET rules, avoiding the need to disclose the full chemical structures. On top of the very large exchange of knowledge, all companies involved synergistically gained approximately 20% more rules from the shared transformations. There is good quantitative agreement between the rules based on shared data compared to both individual companies' rules and rules published in the literature. Known correlations between log D, solubility, in vitro clearance, and plasma protein binding also hold in transformation space, but there are also interesting exceptions. Data pools such as this allow focusing on particular functional groups and characterizing their ADMET profile. Finally the role of a corpus of robustly tested medicinal chemistry knowledge in the training of medicinal chemistry is discussed.

Microwave dielectric heating has become an important method in chemical synthesis and materials processing over the past 15 years, and in the case of the reactions in solutions, there is a well-developed understanding of heating mechanisms and their influence on reaction rate. In the solid-state however, there is much less clarity, despite the advantages to be gained from better insight into the way in which such electromagnetic radiation may couple directly to charge carriers, accelerating reactions in good conductors. The related issue of the influence of microwave irradiation on biological systems, in particular, proteins, and the way in which this may pose hazards to health is similarly poorly understood despite the obvious relevance this may have to the current debate on the influence of electromagnetic radiation, in particular, microwave transmission, on human health. One reason for the paucity of fundamental insight in both fields is because most work has been performed with microwave equipment whose design is derived from that of a domestic oven, and which is not ideal for in situ studies of microwave driven processes. We have been developing new methods of irradiating a variety of solid samples while measuring structural parameters through a range of diffraction techniques, and describe apparatus that will enable X-ray or neutron scattering measurements to be performed on powders or single crystals under microwave irradiation with controlled power level. We also describe preliminary studies of a single crystal of the molecular solid aspirin, and a powder of the microwave-susceptible ionic material BaTiO3, during microwave irradiation.

Tests were conducted at the Paul Ecke Poinsettia Ranch, Encinitas, from Oct 17 - Nov 16’78. The following materials and rates were evaluated: Resmethrin 2E (SPB-1382), Fenvalerate 2.4E (SD-43775), Permethrin 2E (SPB-1513) {all at 0.1, 0.2 and 0.4 lb ai/100 gal) and Oxamyl 2E (Vydate) (0.5, 1.0 and 2.0 lb ai/100 gal). A spreader-sticker, X-77, was added at a rate of 1 ml/gal. Materials were applied until run-off to both sides of bracts and leaves using a 10 gal hydro-piston pump delivering 2.5 gpm (9.5 litres per min) at 100 psi. The C-l red (in 5 inch pots) and Annette Hess variety (in 4 inch pots) were used with 3 replicates/variety/treatment and 10 plants/replicate. Applications were made on 3 dates: l)when plants were well-rooted (ca 3-4 weeks after sticking), 2)when bracts began to show color and flower buds were evident and 3)when 0.5-0.75 in bloom. A commercial application of Temik 10G was applied on C ct 20 at 0.0416g ai/sq ft. Observations on phytotoxicity were made 2,4, and 7 days after each spray application and compared to an untreated control.