Nucleotide receptors in the nervous system. An abundant component using diverse transduction mechanisms

Extracellular nucleotides achieve their role as cell-to-cell communicators by acting at cell surface transmembrane receptors-the P2 receptors. Before molecular cloning led to the isolation of any P2-receptor sequence, a small number of receptor types had been proposed on the basis of pharmacological evidence. The application of molecular biology to this field of receptor research has indicated that a great underestimation of the number of receptor subtypes and of their abundance had occurred. There are now known to be seven characterized P2Y (G protein linked) receptors and the same number again of P2X receptors of the transmitter-gated ion channel type. In this review, we discuss the properties of these cloned receptors, their distribution within the nervous system, and their methods of signal transduction.     

The Drug Involvement Scale for Adolescents (DISA)

This article specifically addressed the need for a multidimensional approach to measuring adolescents' drug involvement. The Drug Involvement Scale for Adolescents (DISA) was theoretically specified and its measurement properties were tested using Confirmatory Factor Analyses and traditional procedures with 705 high-risk and typical high school students. Five first-order dimensions, Drug Access, Alcohol Use, Other Drug Use, Drug Use Control Problems and Adverse Drug Use Consequences, and a hierarchical model of Drug Involvement demonstrated a good fit between model and data. Further, the DISA demonstrated good internal consistency (alpha = .91); correlated as expected with known correlates of adolescent drug use; discriminated drug involvement between high-risk and typical high school students; and predicted later drug involvement and known drug-related consequences among adolescents. The results suggest the DISA should be useful for capturing a multidimensional view of adolescent drug involvement in both etiologic and prevention studies. A major advantage of the DISA is its brevity: twenty-two indicators constructed from twenty-nine items.     

Several parameters of the state of the nervous, immune and endocrine systems in newborn rats exposed to irradiation during the preimplantation period of embryogenesis]

About a decade ago the introduction of predictive testing for Huntington's disease (HD) was an important milestone in medical history. The aim of the present paper concerning predictive DNA-testing for HD is fourfold. First of all it describes the professional challenge of elaborating an adequate test protocol and of permanently using a multidisciplinary approach to deal with predictive test requests. Secondly the paper is aimed at unraveling the factors that play a part in uptake and decision making regarding predictive testing. Hereby the Health Belief Model is used as a framework for understanding differences between tested and untested persons. Thirdly the impact of the test result on psychological well-being is reviewed. Finally this paper assesses the utilisation of prenatal diagnosis after predictive testing for HD and reflects on the psychological and ethical implications of different types of prenatal tests, including preimplantation genetic diagnosis.     

Directional-tip endotracheal tubes for blind nasotracheal intubation

OBJECTIVES: To compare initial success rates of blind nasotracheal intubation using directional-tip endotracheal tubes vs standard endotracheal tubes. METHODS: A prospective trial comparing directional-tip and standard endotracheal tubes during initial attempts at blind nasotracheal intubation (BNTI) at a university hospital ED. Using an alternating schedule, the directional-tip or standard tube was used for the first attempt at BNT1. An attempt was defined as beginning when the tube was placed through the nose into the posterior pharynx and ending when the patient was intubated or the tube was removed from the nares. After the intubation, the physician graded the difficulty of the technique (i.e., easy/routine, intermediate, difficult, or unable to intubate nasally). RESULTS: There were 49 patients entered over 5 months. Patient presentations for the intubations were trauma (45.8%), overdose (33.3%), respiratory/cardiac event (12.5%), seizure (2.1%), and other (6.3%). Intubation was successful on the first attempt in 18 of 21 patients (86%; 95% CI, 64% to 97%) for the directional-tip tube vs 16 of 28 patients (57%; 95% CI, 37% to 76%) for the standard tube (p = 0.03). The groups did not differ in age, sex, clinical presentation, or perceived difficulty of intubation. Only 1 patient could not be intubated nasally and was subsequently intubated orally. CONCLUSION: The use of directional-tip tubes may improve the success rate of the first attempt at BNTI.     

Effects of altering brain cholinergic activity on covert orienting of attention: comparison of monkey and human performance

Experiments were conducted to elucidate the role of the cholinergic neurotransmitter system in arousal and the orienting of attention to peripheral targets. Rhesus monkeys and humans fixated a visual stimulus and responded to the onset of visual targets presented randomly in two visual field locations. The target was preceded by a valid cue (cue and target at the same location), an invalid cue (cue and target to opposite locations), a double cue (cues to both spatial locations, target to one), or, the cue was omitted (no-cue, target to either location). Reaction times (RTs) to the onset of the target were recorded. For monkeys, systemic injections of nicotine (0.003-0.012 mg/kg) or atropine (0.001-0.01 mg/kg), but not saline control injections, reduced mean RTs for all trials, indicating general behavioral stimulation. In addition, nicotine significantly reduced RTs for invalid trials but had little additional effect on those for valid, double, or no-cue trials. Virtually identical effects were observed for human chronic tobacco smokers in performing the same task following cigarette smoking. Injections of atropine in monkeys had no effect on RTs for valid or invalid trials but significantly slowed RTs in double-cue trials that did not require the orienting of attention. These results suggest that in both species, the nicotinic cholinergic system may play a role in automatic sensory orienting. In addition, the muscarinic system may play a role in alerting to visual stimuli in monkeys.     

The effects of wound lavage solutions on canine fibroblasts: an in vitro study

OBJECTIVE: The purpose of this study was to determine the effects of phosphate-buffered saline (PBS), sterile tap water, normal saline, and Ringer's lactate on wound healing in an in vitro model. STUDY DESIGN: The effects of PBS, sterile tap water, normal saline, and Ringer's lactate on a primary line of canine embryonic fibroblasts were determined. ANIMALS OR SAMPLE POPULATION: A primary line of canine embryonic fibroblasts. METHODS: The effects of the various lavage solutions were determined by (1) vital staining of the treated cells with a 0.5% trypan blue solution, (2) evaluation of the amount of lactate dehydrogenase released by the treated cells, and (3) cytopathologic evaluation of hematoxylin and eosin-stained monolayers of treated canine fibroblasts. The cells were exposed to the lavage treatments for the following time intervals: 0.5 minute, 1 minute, 2.5 minutes, 5 minutes, and 10 minutes. PBS was used as the control. RESULTS: Sterile tap water significantly damaged canine fibroblasts at all time intervals (P = .05). This was attributed to the alkaline pH, hypotonicity, and presence of numerous cytotoxic trace elements in the tap water used. Cytotoxic effects were noted in fibroblasts after 10 minutes' exposure to normal saline; this may be because of the acidic pH of normal saline and lack of a buffering system. Ringer's lactate did not induce any significant fibroblast injury. CONCLUSIONS: PBS and Ringer's lactate do not induce any significant fibroblast injury, whereas normal saline and sterile tap water cause mild and severe cytotoxic effects in vitro. CLINICAL RELEVANCE: Further clinical investigation is indicated to establish whether Ringer's lactate is the wound lavage solution of choice compared with normal saline. Sterile tap water may cause considerable fibroblast injury.     

Role of heat shock proteins in the pathogenesis of cystic fibrosis arthritis

BACKGROUND: Arthritis is a well recognised complication of cystic fibrosis. The cause of this arthritis is not yet clear but it is likely to be an immunological reaction to one of the many bacterial antigens to which the lungs are exposed. One such group, the heat shock proteins, (hsp), was investigated. These are immunodominant antigens of a wide variety of infectious microorganisms and have varying amino acid chain sequences, some of which are similar to those found in human tissues. METHODS: Antibodies to human hsp 27 and hsp 90 in the serum of patients with cystic fibrosis, with and without arthritis, and in normal age and sex matched healthy controls were measured. The severity of the cystic fibrosis was assessed by lung function tests and chest radiographs. The nature of the organisms colonising the lungs was determined by bacteriological examination of sputum. RESULTS: Higher mean titres of serum IgG anti-human hsp 27 and hsp 90 antibodies were found in 50 patients with cystic fibrosis than in healthy controls (hsp 27, 0.25 (95% CI 0.19 to 0.33) versus 0.05 (95% CI 0.04 to 0.07); hsp 90, 0.27 (95% CI 0.22 to 0.32) versus 0.11 (95% CI 0.08 to 0.14)). These antibodies were higher in patients in whom the lungs were colonised with Pseudomonas aeruginosa than in those without infection (hsp 27, 0.41 (95% CI 0.17 to 0.63) versus 0.18 (95% CI 0.10 to 0.27); hsp 90, 0.37 (95% CI 0.18 to 0.57) versus 0.22 (95% CI 0.16 to 0.29)). The eight patients with cystic fibrosis with arthritis had higher anti-hsp 27 antibodies (0.48 (95% CI 0.13 to 0.92)) than the 42 patients without arthritis (0.22 (95% CI 0.17 to 0.30)). CONCLUSIONS: These findings suggest that the arthritis associated with cystic fibrosis, despite being seronegative for rheumatoid factor, was associated with more severe lung disease and with a greater inflammatory response to heat shock proteins.     

Breast cancer screening outcomes in women ages 40-49: clinical experience with service screening using modern mammography

The several randomized controlled trials (RCTs) of breast cancer screening among women of ages 40 to 49 now collectively show a statistically significant reduction in breast cancer mortality. However, there have been numerous recent advances in mammography, such that it now is demonstrably better than when the RCTs were conducted. The use of surrogate measures of screening efficacy (tumor size, lymph node status, cancer stage), readily derived from modern service screening programs, demonstrates how the improved mammography of the 1990s should produce a greater degree of mortality reduction among women ages 40-49 than that already demonstrated in the RCTs. Indeed, these surrogate measures of mortality reduction are as favorable for women of ages 40-49 and 65+ as they are for women of ages 50-64, strongly suggesting that, since modern service screening is accepted as effectively reducing mortality among women of ages 50-64, it should also effectively reduce mortality among women in the 40-49 and 65+ age groups.     

A transposable partitioning locus used to stabilize plasmid-borne hydrogen oxidation and trifolitoxin production genes in a Sinorhizobium strain

Improved nitrogen-fixing inoculum strains for leguminous crops must be able to effectively compete with indigenous strains for nodulation, enhance legume productivity compared to the productivity obtained with indigenous strains, and maintain stable expression of any added genes in the absence of selection pressure. We constructed a transposable element containing the tfx region for expression of increased nodulation competitiveness and the par locus for plasmid stability. The transposon was inserted into tetA of pHU52, a broad-host-range plasmid conferring the H2 uptake phenotype. The resulting plasmid, pHUTFXPAR, conferred the plasmid stability, trifolitoxin production, and H2 uptake phenotypes in the broad-host-range organism Sinorhizobium sp. strain ANU280. The broad applications of a transposon conferring plasmid stability are discussed.