Effects of dopaminergic drugs on locomotor activity in teleost fish of the genus Oreochromis (Cichlidae): involvement of the telencephalon

Airpuffs are often used as blink reflex eliciting stimuli, but the airpuff makes an abrupt noise when it leaves the tube. The present study investigated the effects of the tactile and acoustic components of airpuffs on the blink reflex in 18 human subjects. Subjects received airpuffs to the temple at 10.3, 20.7 and 31.0 kPa in a within-subjects design. The airpuff-associated noise was attenuated (Airpuff + Attenuated noise) or airpuffs were presented without noise-attenuation (Airpuff+ Unattenuated noise) in two conditions. In the third condition, the airpuff was directed away from the temple to eliminate the tactile component of the airpuff (Noise alone). Reflexes were larger, more probable and faster to the Airpuff+ Unattenuated noise compared to the Airpuff+ Attenuated noise. This indicates that there is an excitatory influence from the acoustic component of the airpuff. The findings suggest that researchers should reduce the acoustic component of airpuffs in studies that use airpuffs as reflex eliciting stimuli.     

Agonist-induced endocytosis and recycling of the gonadotropin-releasing hormone receptor: effect of beta-arrestin on internalization kinetics

This study examined the dynamics of endocytotic and recycling events associated with the GnRH receptor, a unique G protein-coupled receptor (GPCR) without the intracellular carboxyl-terminal tail, after agonist stimulation, and investigated the role of beta-arrestin in this process. Subcellular location of fluorescently labeled epitope-tagged GnRH receptors stably expressed in HEK 293 cells was monitored by confocal microscopy, and the receptor/ligand internalization process was quantified using radioligand binding and ELISA. Agonist stimulation resulted in reversible receptor redistribution from the plasma membrane into the cytoplasmic compartment, and colocalization of internalized GnRH receptors with transferrin receptors was observed. Internalization experiments for the GnRH receptor and another GPCR possessing a carboxy-terminal tail, the TRH receptor, showed that the rate of internalization for the GnRH receptor was much slower than for the TRH receptor when expressed in both HEK 293 and COS-7 cells. TRH receptor internalization could be substantially increased by coexpression with beta-arrestin in COS-7 cells, while GnRH receptor internalization was not affected by coexpression with beta-arrestin in either cell type. Coexpression of the GnRH receptor with the dominant negative beta-arrestin (319-418) mutant did not affect its ability to internalize, and activated GnRH receptors did not induce time-dependent redistribution of beta-arrestin/green fluorescent protein to the plasma membrane. However, the beta-arrestin mutant impaired the internalization of the TRH receptor, and activated TRH receptors induced the beta-arrestin/green fluorescent protein translocation. This study demonstrates that, despite having no intracellular carboxy-terminal tail, the GnRH receptor undergoes agonist-stimulated internalization displaying distinctive characteristics described for other GPCRs that internalize via a clathrin-dependent mechanism and recycle through an acidified endosomal compartment. However, our data indicate that the GnRH receptor may utilize a beta-arrestin-independent endocytotic pathway.     

Pediatric penetrating thoracic trauma: a five-year experience

Penetrating thoracic trauma is managed nonoperatively in 85% of adult patients. We hypothesized that similar trauma in children would lead to proportionately more vital tissue damage and a higher rate of operative intervention. The pediatric penetrating thoracic trauma experience of a level one trauma center was analyzed over a five-year period. Data reviewed included circumstances of injury, Pediatric Trauma Score (PTS), interventions performed, and outcome. Of 61 children with thoracic trauma, 13 had penetrating injuries. Of these 13, seven were unintentional (five from firearms); the rest were caused by assaults. Seven patients (54%) underwent thoracotomy or laparotomy. All five patients with a PTS < 8 underwent surgical intervention, whereas only two of the eight patients with a PTS > or = 8 needed surgery (P < 0.05). There was one death. We reached the following conclusions: 1) Children with penetrating thoracic trauma are more likely to require surgical intervention than adults. 2) Penetrating thoracic trauma in children should elicit a thorough search for operative lesions. 3) About half these injuries are unintentional, and thus potentially preventable.     

Postmortem changes in blood amitriptyline concentration

Detailed toxicological studies were undertaken on two suicides by amitriptyline overdose, one with salicylate also. In the first case, 10 initial blood samples taken 21 h after body discovery and an estimated 28 1/2 h after overdose had drug concentration (mg/L) ranges of 2.5-12 for amitriptyline (AM), 0.7-3.1 for nortriptyline (NOR), and 81-244 for salicylate (SAL). Ten blood samples taken 42 h later showed corresponding ranges of 1-39 AM, 0.6-7.0 NOR, and 86-310 SAL. Sample haemoglobin concentrations (range, 8.7-23.5 g/dl) did not correlate with drug concentrations. Postmortem increase in pulmonary vein AM concentration occurred more rapidly than in the pulmonary artery, likely reflecting relative ease of diffusion across the vessel walls from lung (AM, 60 mg/kg). In nine tissue samples, drug concentrations (mg/kg) were highest in the liver: AM, 301; and SAL, 670. Considerable drug residue was present in gastric contents, duodenal contents, and seven sequential small bowel contents. In both cases, sanguineous putrefactive pleural fluid showed higher AM concentrations on the left than on the right (2.0 vs 1.4 and 23 vs 16), likely reflecting diffusion from gastric drug residue. The detailed case data illustrate the intensity and complexity of postmortem drug diffusion from reservoirs in solid organs, such as the lungs, and unabsorbed gastric residue, into the blood and putrefactive fluids.     

Sonolucent peripancreatic masses: differential diagnosis and related imaging

The third variable region (V3) of the HIV-1 gp120 envelope molecule appears to represent a target for naturally occurring neutralizing antibodies in HIV-1-infected individuals. In this report, we examined the extent of antibody cross-reactivity to a panel of V3-based synthetic peptides in six inbred strains of mice following repeated immunization with a baculovirus-derived recombinant gp160 (rgp160) preparation formulated with alum. The amino acid sequence of the rgp160 used in these immunizations was based upon the HIV-1 IIIB (LAI) isolate. Following five injections with rgp160, all six strains developed antibodies to the homologous IIIB-based V3 peptides, designated 304-321 and RP135. However, antibody cross-reactivity to the other nonhomologous V3 peptides was either undetectable or limited among the strains of mice examined. No in vitro neutralizing activity against HIV-1 was observed in sera from any of the six inbred strains of mice that were examined. These results suggest that repeated immunization of mouse strains with a rgp160/alum formulation leads to nonneutralizing antibodies directed against the V3 region which remain predominantly type specific.     

Interrelationships between crime, substance abuse, and aggressive behaviours among persons with traumatic brain injury

Professionals have suggested that aggressiveness, substance abuse, and criminality contribute to poor outcomes after brain injury. There is considerable research regarding post-injury aggressive behaviour, but limited information concerning criminal behaviour and alcohol use patterns. With a sample of 327 patients varying in severity of traumatic brain injury, the present investigation examined alcohol use patterns, arrest histories, behavioural characteristics, and psychiatric treatment histories. Relative to the uninjured population, analysis revealed relatively high incidence of heavy drinking, both pre- and post-injury, among patients with a history of arrest. Increases in abstinence rates were found regardless of arrest history. In addition, a history of arrest was associated with a greater likelihood of psychiatric treatment. Findings also indicated relatively high levels of aggressive behaviours. Discussion focuses on implications for evaluation, rehabilitation, and future research.     

Cardiac psychophysiology and autonomic space in humans: Empirical perspectives and conceptual implications.

Contemporary findings reveal that autonomic control of dually innervated visceral organs does not lie along a single continuum extending from parasympathetic to sympathetic dominance. Rather, a bivariate autonomic space bounded by sympathetic and parasympathetic axes is the minimal representation necessary to capture the modes of autonomic control. A quantitative bivariate model for the chronotropic control of the heart in humans is empirically instantiated. This model provides a more comprehensive characterization of psychophysiological response than simple measures of end-organ state and permits a differentiation of behavioral states and processes that would otherwise remain obscure. The model also illuminates and subsumes general principles such as the law of initial values and reveals a fundamental physiological rationale for the selection of heart period over heart rate as a metric for cardiac chronotropy. The present article also considers strategies for psychophysiological investigations within the autonomic space model, the limitations of these methods, and analytical tools for assessing their validity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Virus-specific interaction between the human cytomegalovirus major capsid protein and the C terminus of the assembly protein precursor

We previously identified a minimal 12-amino-acid domain in the C terminus of the herpes simplex virus type 1 (HSV-1) scaffolding protein which is required for interaction with the HSV-1 major capsid protein. An alpha-helical structure which maximizes the hydropathicity of the minimal domain is required for the interaction. To address whether cytomegalovirus (CMV) utilizes the same strategy for capsid assembly, several glutathione S-transferase fusion proteins to the C terminus of the CMV assembly protein precursor were produced and purified from bacterial cells. The study showed that the glutathione S-transferase fusion containing 16 amino acids near the C-terminal end was sufficient to interact with the major capsid protein. Interestingly, no cross-interaction between HSV-1 and CMV could be detected. Mutation analysis revealed that a three-amino-acid region at the N-terminal side of the central Phe residue of the CMV interaction domain played a role in determining the viral specificity of the interaction. When this region was converted so as to correspond to that of HSV-1, the CMV assembly protein domain lost its ability to interact with the CMV major capsid protein but gained full interaction with the HSV-1 major capsid protein. To address whether the minimal interaction domain of the CMV assembly protein forms an alpha-helical structure similar to that in HSV-1, peptide competition experiments were carried out. The results showed that a cyclic peptide derived from the interaction domain with a constrained (alpha-helical structure competed for interaction with the major capsid protein much more efficiently than the unconstrained linear peptide. In contrast, a cyclic peptide containing an Ala substitution for the critical Phe residue did not compete for the interaction at all. The results of this study suggest that (i) CMV may have developed a strategy similar to that of HSV-1 for capsid assembly; (ii) the minimal interaction motif in the CMV assembly protein requires an alpha-helix for efficient interaction with the major capsid protein; and (iii) the Phe residue in the CMV minimal interaction domain is critical for interaction with the major capsid protein.     

Elevated prostaglandin E2 production by monocytes is responsible for the depressed levels of natural killer and lymphokine-activated killer cell function in patients with breast cancer

BACKGROUND: Human natural killer (NK) cells mediate spontaneous cytotoxicity against tumor cells and represent the main precursors of lymphokine-activated killer (LAK) cell activity. A comparison of some aspects of NK and LAK cell activity was undertaken in 85 preoperative patients with breast cancer and 75 healthy donors. METHODS: NK cell activity (tested in 18-hour cultures of effector peripheral blood mononuclear cells [PBMC] with K562 or MOLT-4 tumor target cells) was significantly diminished in these patients as it was the fully mature LAK cell activity (i.e., interleukin-2 (IL-2)-induced cytotoxicity in PBMC) against NK resistant target cells. Using immunoenzymatic methods we showed that the reduced NK cell activity was due to abnormally high levels of prostaglandin E2 (PGE2) produced by monocytes in culture. RESULTS: PGE2 was found to suppress the production of IL-2 in these cultures. Removal of monocytes from PBMC restored to almost normal levels the deficient NK and LAK cell activity in patients with breast cancer and was also associated with a normalization in the levels of PGE2 and IL-2. Indomethacin and gamma-interferon (IFN-gamma) increased the NK and LAK cell activity in these patients up to the levels of healthy donors. When highly purified CD56+ cells (obtained by an immunomagnetic isolation technique) were used as effector cells, no differences in LAK cell activity could be noticed between healthy donors and patients with cancer. FACS and northern blot analyses demonstrated a PGE2-mediated down-regulation of IL-2 receptor (IL-2R) expression on CD56+ cells that correlated with reduced LAK cell activity. This inhibitory effect of PGE2 was noticeable in long-term LAK cultures and was abrogated in the presence of IFN-gamma or indomethacin. CONCLUSION: This study may have important implications in the potentiation of NK and LAK cell activity for immunotherapeutic protocols in patients with breast cancer.     

Bacterial and viral parenchymal infections of the brain

We reviewed the literature addressing the use and complications associated with low-viscosity distention fluids in urologic and hysteroscopic procedures. The possible causes of fluid complications included elevated intrauterine pressure, myometrial invasion, prolonged operating time, and operative trauma to the cervix or uterine body. Physiologic electrolyte solutions create only fluid overload, and treatment requires cardiovascular support and diuresis. Nonelectrolytic solutions result in acute dilutional hyponatremia, which has been referred to as the transurethral resection of the prostate syndrome. Treatment requires diuresis and a rapid, controlled return of the serum sodium level to 120-130 mmol. These complications can be minimized with proper use of equipment and careful monitoring of fluid volumes. To recognize and treat them, the surgeon must be knowledgeable about the fluid being used and the difficulties it may cause.