PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor

Eph-related receptor tyrosine kinases (RTKs) have been implicated in intercellular communication during embryonic development. To elucidate their signal transduction pathways, we applied the yeast two-hybrid system. We could demonstrate that the carboxyl termini of the Eph-related RTKs EphA7, EphB2, EphB3, EphB5, and EphB6 interact with the PDZ domain of the ras-binding protein AF6. A mutational analysis revealed that six C-terminal residues of the receptors are involved in binding to the PDZ domain of AF6 in a sequence-specific fashion. Moreover, this PDZ domain also interacts with C-terminal sequences derived from other transmembrane receptors such as neurexins and the Notch ligand Jagged. In contrast to the association of EphB3 to the PDZ domain of AF6, the interaction with full-length AF6 clearly depends on the kinase activity of EphB3, suggesting a regulated mechanism for the PDZ-domain-mediated interaction. These data gave rise to the idea that the binding of AF6 to EphB3 occurs in a cooperative fashion because of synergistic effects involving different epitopes of both proteins. Moreover, in NIH 3T3 and NG108 cells endogenous AF6 is phosphorylated specifically by EphB3 and EphB2 in a ligand-dependent fashion. Our observations add the PDZ domain to the group of conserved protein modules such as Src-homology-2 (SH2) and phosphotyrosine-binding (PTB) domains that regulate signal transduction through their ability to mediate the interaction with RTKs.     

Further analysis of the reliability of the posterior tangent lateral lumbar radiographic mensuration procedure: concurrent validity of computer-aided X-ray digitization

OBJECTIVE: To investigate the reliability of a specific method of radiographic analysis of the geometric configuration of the lumbopelvic spine in the sagittal plane, and to investigate the concurrent validity of a computer-aided digitization procedure designed to replace the more tedious and time-consuming manual measurement process. DESIGN: A blind, repeated-measures design was used. The results of radiographic measures derived through the traditional manual marking method were compared with measures derived by computer-aided digitization of lateral lumbopelvic radiographs. SETTING: Private chiropractic clinic. MAIN OUTCOME MEASURES: Pearson's product-moment correlation coefficients, paired sample t tests and intraclass correlation co-efficients (ICC) were used to examine intraexaminer reliability, and repeated measures of analysis of variance were used to examine interexaminer reliability for relative rotation angles for T12-L1, L1-L2, L2-L3, L3-L4, L4-L5, L5-S1, overall lordosis measurement [absolute rotation angle (ARA)] from L1-L5 and Cobb angle of overall lordosis measured from the inferior surface of T12 to the superior surface of S1, Ferguson's sacral base angle to horizontal, angle of pelvic tilt (arcuate angle) to horizontal and anteroposterior thoracic translation (Sz) in millimeters. RESULTS: ICC estimates for intraexaminer reliability were in the range of 0.96-0.98 for the L1-L5 ARA, a range of 0.87-0.99 for the arcuate angle measurement, 0.83-0.94 for the Ferguson's angle measurement, 0.88-0.95 for the Cobb angle measurement from the inferior surface of T12 compared with the superior surface of S1 and 0.98-1.00 for the translation measurement of the lower thoracic spine to S1 (Sz). The intersegmental measurement's (T12-L1, L1-L2, L2-L3, L3-L4, L4-L5, L5-S1) correlations ranged from a low of 0.55 to a high of 0.97. Examination of these findings suggests that the reliability for the three doctors is acceptable with only the T12-L1 intersegmental measure falling below 0.70 for the least experienced examiner. Average ICC of interexaminer reliability for manual and computer-aided digitizing examiners were the following: 0.96 for the L1-L5 ARA; 0.84 for the arcuate angle measurement; 0.82 for the Ferguson's angle measurement; 0.88 for the Cobb angle measurement; 1.00 for the Sz translation measurement; and values of 0.65, 0.73, 0.74, 0.75, 0.89 and 0.81 for relative rotation angle measurements T12-L1, L1-L2, L2-L3, L3-L4, L4-L5 and L5-S1, respectively. CONCLUSION: The data tend to support the reliability of this method of radiographic analysis of the geometric configuration of the lumbopelvic spine as viewed on lateral lumbopelvic radiographs. The additional data presented here tend to support the concurrent validity of the computer-aided digitization method of analysis inasmuch as the measures determined by the digitizing examiners are essentially identical to those determined by the manual method plus or minus the average standard error of measure of each value.     

Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA

OBJECTIVE: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. EVIDENCE: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. PROCESS: The panel was convened in February 1997 and met regularly through November 1997. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included.     

Social-emotional characteristics of preschool-aged children referred for Child Find screening and assessment: a comparative study

In order to determine changes in breathing patterns brought about by resistive loading, ventilation was recorded in 11 healthy subjects with four linear resistances (3.57, 5.75, 8.76 and 13.13 cmH2O L(-1) sec) added in a random order throughout the entire breath. At steady state, a breath-by-breath analysis of airflow was used to quantify the pattern of breathing in terms of respiratory variables: TI, TE, Tt, VT, VT/TI, TI/Tt, and by taking TI, TE, VT all together (TRIAD) and also the shape of the entire airflow profile quantified by harmonic analysis (ASTER). Group analysis using ANOVA showed significant changes in all variables. There were increasing changes with increasing loads in all variables, the smallest changes being in TI/Tt. Within to between-individual comparisons between two loads showed that only TI/Tt and the ASTER were more similar within than between-individuals for all comparisons. It was concluded that at steady state mechanisms of load compensation come into play inducing changes in the pattern of breathing proportional to the loads while maintaining some of the individual characteristics.     

Amount of training affects associatively-activated event representation

The effects of variations in the amount of training on behavioral plasticity were examined in three experiments that used appetitive Pavlovian conditioning procedures with rats. In experiments 1 and 2, an auditory conditioned stimulus (CS) substituted for a food unconditioned stimulus (US) in the acquisition of new learning about the food US after small numbers of CS-US pairings, but not after larger numbers of pairings. After limited exposure to the relation between the auditory CS and food, pairings of the CS with the toxin LiCl, in the absence of food, were sufficient to establish an aversion to the food US that was previously paired with that CS. This CS-mediated learning did not occur after more extensive exposure to the CS-food relation. In contrast, in experiment 3. mediated performance of previously-established conditioned responding was unaffected by the number of CS-US pairings used to establish that performance. Conditioned responding to the auditory CS remained sensitive to post-training devaluation of the food US regardless of the amount of initial CS-US training. Implications of these results for the investigations of cortical and other brain mechanisms of behavioral plasticity are discussed.     

Blood levels of insulin-like growth factors I and II in neonates of non-insulin-dependent diabetic rats

Immobilization bone loss, whether due to whole body immobilization or local causes, is associated with an initial rapid phase of trabecular bone loss, but the long-term effects of immobilization on cortical bone are not well described. We have studied metacarpal morphometry in 16 men who had undergone partial or complete traumatic digital amputations 4-71 years earlier. Noninvolved metacarpals from the affected and unaffected hands were used as controls. Cortical bone width was significantly reduced in the metacarpals proximal to the amputated digits (P = 0.001). In the 7 subjects who suffered amputation before the age of 19, the cortical bone deficit was primarily due to a reduction in the total width of the medullary shaft (P = 0.007), whereas medullary width was not changed. In these subjects the metacarpal was also significantly reduced in length, by a mean 2.9 mm (P = 0.35). In the 9 subjects who had their amputation after the age of 19, both a reduction in total width and an increase in medullary width (P = 0.017) accounted for the cortical bone deficit. The deficit in total width was related to the time since amputation (P = 0.008) and could be accounted for by loss of the normal age-related increase in total width (0.01 mm/year). We conclude that in this model of immobilization osteoporosis, the metacarpal proximal to the amputated digit demonstrates cortical osteopenia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parotid lipomatosis

A case of parotid lipomatosis is reported, and the literature is reviewed. This rare condition presents as a slow growing parotid mass, which may be diagnosed preoperatively using computed tomography or magnetic resonance imaging. Long-term clinical follow-up is important because apparently complete surgical excision may be complicated by recurrence.     

Comparative analysis of breast cancer contamination in mobilized and nonmobilized hematopoietic grafts

We report a case of an 18-month-old female who presented with three supernumerary upper limbs of varying lengths on the right side. Each limb had a proximal, middle, and distal segment, and an intercalated elbow and wrist joint. A single digit was present in the superior limb, three digits in the middle limb, and two digits in the caudal-most limb. Right plagiocephaly, congenital torticollis, scoliosis involving the upper and mid thoracic region, and a hypoplastic right pectoralis major were the other abnormal features noted. Radiography showed two scapulae, humerus, a single forearm bone in each limb, and rudimentary metacarpals and phalanges. Limb duplication may rarely be encountered in parasitic conjoined twins. The role of mutagens, drugs, cellular contributions, and morphogens in the growth and differentiation of limbs has been studied in animals. It is rather difficult to deduce the time of action of the factors responsible for such a malformation.     

Assessing motivation for change: Preliminary development and evaluation of a scale measuring the costs and benefits of changing alcohol or drug use.

This article describes the construction and preliminary evaluation of a scale (the Alcohol and Drug Consequences Questionnaire [ADCQ]) assessing the costs and benefits of changing an alcohol or drug problem. The ADCQ's costs and benefits subscales displayed good internal reliability (Cronbach alphas were .90 for the benefits subscale and .92 for the costs subscale). Furthermore, the ADCQ was significantly related to respondents' ratings of the importance of achieving their alcohol or drug treatment goal and to drinking at a 12-month follow-up. Measures assessing the costs and benefits of change appear to be useful indexes of client motivation and for predicting long-term change within the addictions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)