Potent dipeptide inhibitors of the pp60c-src SH2 domain.

The design, synthesis, and evaluation of dipeptide analogues as ligands for the pp60c-src SH2 domain are described. The critical binding interactions between Ac-Tyr-Glu-N(n-C5H11)2 (2) and the protein are established and form the basis for our structure-based drug design efforts. The effects of changes in both the C-terminal (11-27) and N-terminal (51-69) portions of the dipeptide are explored.

Dual inhibition of human type 4 phosphodiesterase isostates by (R, R)-(+/-)-methyl 3-acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3- methyl-1-pyrrolidinecarboxylate.

Purified recombinant human type 4 phosphodiesterase B2B (HSPDE4B2B) exists in both a low- and a high-affinity state that bind (R)-rolipram with Kd's of ca. 500 and 1 nM, respectively [Rocque, W. J.

Detection of soft X-rays and a sensitive search for noble gases in comet Hale-Bopp.

An image of comet Hale-Bopp (C/1995 O1) in soft x-rays reveals a central emission offset from the nucleus, as well as an extended emission feature that does not correlate with the dust jets seen at optical wavelengths. Neon was found to be depleted in the cometary ice by more than a factor of 25 relative to solar abundance, which suggests that ices in Hale-Bopp formed at (or later experienced) temperatures higher than 25 kelvin. A helium line emission at a wavelength of 584 angstroms was detected and may be attributable to charge transfer of solar wind alpha particles in the cometary coma.

The activity and size of the nucleus of comet Hale-Bopp (C/1995 O1) [see comment].

Analysis of Hubble Space Telescope (HST) images of comet Hale-Bopp (C/1995 O1) suggests that the effective diameter of the nucleus is between 27 to 42 kilometers, which is at least three times larger than that of comet P/Halley. The International Ultraviolet Explorer and HST spectra showed emissions from OH (a tracer of H2O) and CS (a tracer of CS2) starting in April 1996, and from the CO Cameron system (which primarily traces CO2) starting in June 1996. The variation of the H2O production rate with heliocentric distance was consistent with sublimation of an icy body near its subsolar point.

Loss of gap junction plaques and inhibition of intercellular communication in ilimaquinone-treated BICR-M1Rk and NRK cells.

To examine the mechanism(s) and pathways of gap junction formation and removal a novel and reversible inhibitor of protein secretion, ilimaquinone (IQ), was employed. IQ has been reported to cause the vesiculation of Golgi membranes, block protein transport at the cis-Golgi and depolymerize cytoplasmic microtubules. Connexin43 (Cx43) immunolabeling and dye microinjection experiments revealed that gap junction plaques were lost and intercellular communication was inhibited following IQ treatment for 1 hr in BICR-M1Rk rat mammary tumor cells and for 2 hr in normal rat kidney (NRK) cells.

Attitudes toward obstetrics training. Residents surveyed at McGill University and University of Montreal.

Objective: To determine family medicine residents' attitudes toward family practice training in obstetrics and neonatology before and after implementation of a modified obstetrics curriculum at McGill University (MG).

Design: Two-group pretest and posttest. Fifty-seven respondents, 31 at MG, 26 at University of Montreal (UM), were case matched as first-year and second-year residents.

Eye movement desensitisation treatment utilises the positive visceral element of the investigatory reflex to inhibit the memories of post-traumatic stress disorder: a theoretical analysis.

Background: Eye movement desensitisation and reprocessing (EMDR) has attracted controversy and has led to publications covering a wide range of psychological problems treated by EMDR, in particular, post-traumatic stress disorder (PTSD). There is growing clinical evidence of the effectiveness of EMDR, but a lack of a convincing theoretical basis to explain its rapid effect.

Method: This paper argues that a combination of Pavlovian and Darwinian theory provide a theoretical explanation for the therapeutic effectiveness of EMDR.

Medicaid-funded home care for the frail elderly and disabled: evaluating the cost savings and outcomes of a service delivery reform.

Objectives: In response to rising demand and increased costs for home care services for frail elderly and disabled Medicaid clients, New York City implemented cluster care, a shared-aide model of home care. Our objective: to evaluate the effects of cluster care on home care hours and costs, client functioning, depressive symptoms, and satisfaction.

Data Sources: Client interviews, conducted prior to implementation and again 16 months later; Medicaid claims records; home attendant payroll files; and vendor agency records.

Fluorescent hydroxyl emissions from Saturn's ring atmosphere.

Just before earth passed through Saturn's ring plane on 10 August 1995, the Hubble Space Telescope Faint Object Spectrograph detected ultraviolet fluorescent emissions from a tenuous atmosphere of OH molecules enveloping the rings. Brightnesses decrease with increasing distance above the rings, implying a scale height of about 0.45 Saturn radii (Rs).

Contact dermatitis associated with the use of Always sanitary napkins.

Objective: To report a clinical association between vulvar irritation or contact dermatitis and the use of Always sanitary napkins.

Design: Case series.

Setting: A gynecology practice in Montreal.

Cardiovascular effects of Leu-enkephalin in the nucleus tractus solitarius of the rat.

Microinjections of Leu-enkephalin into the dorsal vagal complex induced hypotension and bradycardia. Both naloxone, given at a dose conferring selectivity for mu receptors, and the delta antagonist ICI 154,129 prevented the cardiovascular effects of Leu-enkephalin. Naloxone was also found to decrease the gain of the baroreflex.

Effects of serotonin-1 and serotonin-2 receptor agonists on neuronal activity in the nucleus tractus solitarius.

Spontaneous neuronal activity in the solitary tract nucleus was recorded extracellularly in a brain slice preparation during bath-application of 5-HT1 and 5-HT2 receptor-selective agonists and antagonists. The 5-HT1A/5-HT1B agonist 5-carboxamidotryptamine depressed activity in 20 of 25 neurons studied. The remaining five neurons were unaffected.

Design and synthesis of conformationally constrained analogues of 4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro 20-1724) as potent inhibitors of cAMP-specific phosphodiesterase.

The synthesis and biological evaluation of cAMP-specific phosphodiesterase (PDE IV) inhibitors is described. The PDE IV inhibitor 4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro 20-1724, 2) was used as a template from which to design a set of rigid oxazolidinones, imidazolidinones, and pyrrolizidinones that mimic Ro 20-1724 but differ in the orientation of the carbonyl group. The endo isomer of each of these heterocycles was more potent than the exo isomer in an enzyme inhibition assay and a cellular assay, which measured TNF alpha secretion from activated human peripheral blood monocytes (HPBM).

Vacuum-ultraviolet quantum efficiency of a thinned, backside-illuminated charge-coupled device.

The UV quantum efficiency of a Scientific Imaging Technologies (SITe, Beaverton, Ore., formerly Tektronix) 1024 pixel by 1024 pixel thinned and backside-illuminated charge-coupled device has been measured in the wavelength band from 1164 to 5200 Å. The 24-µm-pixel device, which does not have an antireflective coating, has an average quantum efficiency of more than 40% in the band from 1164 to 4000 Å and a read noise of 15 e(-)/pixel.

Cardiovascular effects of serotonin in the nucleus of the solitary tract.

The cardiovascular regulatory role of serotonin [5-hydroxytryptamine (5-HT)] in the solitary tract nucleus (NTS) was investigated in urethan-anesthetized Wistar rats. Unilateral microinjection of 5-HT (5 nmol in 50 nl) into the NTS evoked depressions of both arterial pressure (-20 +/- 1 mmHg) and heart rate (-43 +/- 6 beats/min). Induction of bradycardia and hypotension was repeatable and consistently obtained with injections into the NTS but not into neighboring structures.