Insulin-like growth factor-binding protein 1 stimulates human trophoblast migration by signaling through alpha 5 beta 1 integrin via mitogen-activated protein Kinase pathway

A highly migratory subpopulation of the human placental trophoblast, known as the extravillous trophoblast (EVT), invades the uterus and its vasculature, to establish adequate exchange of key molecules between the maternal and fetal circulations. During their formation, EVT cells selectively acquire alpha 5 beta 1 integrin. We had shown that alpha 5 beta 1 is required for their migratory function, and that EVT cell migration is stimulated by insulin-like growth factor-binding protein (IGFBP)-1 produced by the uterine decidua. The present study examined whether this stimulation is dependent on binding of the Arg-Gly-Asp (RGD) domain of IGFBP-1 to an RGD binding site on the alpha 5 beta 1 integrin, followed by activation of focal adhesion kinase (FAK) and stimulation of the mitogen-activated protein kinase (MAPK) pathway. IGFBP-1 treatment increased migration of EVT cells, whereas an anti-alpha 5 beta 1 integrin antibody blocked migration regardless of IGFBP-1 treatment. Migration stimulation by IGFBP-1 was abrogated by pretreatment with a Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), but not a Gly-Arg-Gly-Glu-Ser-Pro (GRGESP) hexapeptide, and by mutation of the RGD domain of IGFBP-1 to Trp-Gly-Asp (WGD). IGFBP-1 treatment caused a rapid localization of immunoreactive FAK to cellular lamellipodia, a rapid increase in phosphorylation of FAK and extracellular-signal regulated kinases 1 and 2. Preincubation of EVT cells with Herbimycin A, a tyrosine kinase inhibitor, abrogated IGFBP-1 effects; whereas an MAPK kinase inhibitor, PD 98059, reduced migration regardless of IGFBP-1 treatment. These results indicate that IGFBP-1 stimulation of EVT cell migration occurs by binding of its RGD domain to the alpha 5 beta 1 integrin, leading to activation of FAK and stimulation of MAPK pathway.     

Evaluating the febrile patient with a rash

The differential diagnosis for febrile patients with a rash is extensive. Diseases that present with fever and rash are usually classified according to the morphology of the primary lesion. Rashes can be categorized as maculopapular (centrally and peripherally distributed), petechial, diffusely erythematous with desquamation, vesiculobullous-pustular and nodular. Potential causes include viruses, bacteria, spirochetes, rickettsiae, medications and rheumatologic diseases. A thorough history and a careful physical examination are essential to making a correct diagnosis. Although laboratory studies can be useful in confirming the diagnosis, test results often are not available immediately. Because the severity of these illnesses can vary from minor (roseola) to life-threatening (meningococcemia), the family physician must make prompt management decisions regarding empiric therapy. Hospitalization, isolation and antimicrobial therapy often must be considered when a patient presents with fever and a rash.     

Comparison of Cytology and Cervkography in Screening a High Risk Australian Population for Cervical Human Papillomavirus and Cervical intraepithelial Neoplasia

Summary: Two different screening methods, the Papanicolaou (Pap) smear and cervigram were compared in screening 245 Sydney women over a 6-month period in 1988 at a city sexually transmitted diseases (STD) centre, for cervical human papillomavirus (HPV), cervical intraepithelial neoplasia (CIN) and cervical cancer. The Pap smear through the identification of cytologically abnormal cells correctly detected 54% of cases of histologically proven CIN and 39.2% of cases of HPV. The cervigram through the identification of acetowhite epithelium and/or abnormal vessels on the cervix correctly detected 64% of cases of histologically proven CIN and 70.6% of cases of HPV. However, when both tests were used together, 92% of CIN lesions and 82.4% of HPV lesions were correctly identified. Histology of a colposcopically directed biopsy was used as the 'gold standard'. The sensitivity and specificity of the Pap smear after correction for verification bias was 46% and 78% respectively, and for the cervigram was 49% and 60% respectively. Hence neither screening test appears adequate on its own, at least in an STD population.     

Perinatal stimulation and adaptation of the neonate

The present report describes psychobiological studies of behavior around the time of birth. An adaptive, ecological perspective is presented in which stimulation of the fetus and newborn is purported to instigate adaptive postpartum behavior. Studies describing the perinatal sensory environment are reviewed, with a consideration of emergent sensory function of the fetus. It is asserted that afferent input associated with parturition perturbs the fetus and neonate, producing a general arousal state that facilitates breathing, suckling, and early learning. The view developed herein is that perinatal sensory input induces and canalizes the newborn's behavior, thereby regulating adaptive postpartum function. Deviations in afferent input may alter ontogenetic trajectories and compromise developmental outcome by reducing availability of conditions necessary for adequate postpartum adaptation.     

Abnormal anatomy of the lumbosacral region imaged by magnetic resonance in children with anorectal malformations

OBJECTIVE: To investigate the frequency of lumbosacral anomalies, the association with urogenital abnormalities, and the correlation with defaecation pattern by magnetic resonance imaging (MRI). METHODS: A prospective analysis was performed of routine MRI in patients with anorectal malformations. Between 1990 and 1994, MRI was performed in 43 such patients: 31 boys and 12 girls. Twenty four had a high anorectal malformation, 16 had a low anorectal malformation, and three had Currarino's triad. MRI was performed before reconstruction in 26, and postoperatively in 17. Urogenital anomalies were found in 21. RESULTS: Abnormalities of the spinal cord and spine were found with MRI in 20 patients (46.5%); caudal regression syndrome in 10, tethered cord in two, a combination of both in three, and other spinal anomalies in five. These anomalies were found in 30% of the patients with low anorectal malformations, and in 50% with high anorectal malformations. In patients with urogenital malformations, MRI more often showed spinal anomalies (13/21, 62%) than in patients without (7/22, 32%). In high anorectal malformations, defaecation was more often a problem in patients with spinal anomalies (12/15, 80%) than in patients without (2/8, 25%). CONCLUSIONS: Spinal anomalies in the lumbosacral region were found with MRI in 46.5% of patients with anorectal malformations. Since presence of these anomalies seems to be related to clinical outcome, MRI should be performed routinely in all such patients.     

Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

Radiofrequency power deposition utilizing thermal imaging.

Wavelength effects influence radiofrequency (RF) power deposition distributions and limit magnetic resonance (MR) medical applications at very high magnetic fields. The power depositions in spherical saline gel phantoms were deduced from proton resonance shift thermal maps at both 1.5 T and 3.0 T over a range of conductivities. Phase differences before and after RF heating were measured for both a quadrature head coil and a circular surface coil. A long echo time (TE) pulse sequence with a 3D phase unwrap algorithm provided increased thermal sensitivity. The measured thermal maps agreed with a model of eddy-current heating by circularly polarized oscillating RF fields in a conducting dielectric sphere. At 3.0 T, thermal maps were acquired with a <0.32 degrees C temperature rise at 4 W. Proton resonance shift thermal maps provided a measure of hot spots in very-high-field MR imaging (MRI), in which both the phase sensitivity and signal-to-noise ratio (SNR) were increased. The method provides a means of studying the heat distribution generated by RF coils excited by clinical pulse sequences.