The duration of phorbol-inducible ErbB2 tyrosine dephosphorylation parallels that of receptor endocytosis rather than threonine-686 phosphorylation: implications for the physiological role of protein kinase C in growth factor receptor signalling

Tumour cell growth may be accelerated by protein kinase C (PKC) agonists such as phorbol esters and receptor tyrosine kinases, but receptor tyrosine kinases are in turn desensitized to growth factors by PKC agonists. To clarify this apparent PKC bifunctionality, we have used phosphoantibodies to determine the relationship between PKC- dependent phosphorylation events affecting the ErbB2 oncoprotein in G8/DHFR 3T3 cells. Neither the kinetics nor the extent of phorbol- induced juxtamembrane domain (Thr686) phosphorylation vary directly with C-terminal (Tyr1222) dephosphorylation, with Tyr1222 continuing to be dephosphorylated long after Thr686 phosphorylation has also declined. Platelet-derived growth factor (PDGF) mimics the short-term effects of phorbol on Thr686 and Tyr1222 phosphorylation, and confocal microscopy reveals that both of these PKC agonists induce rapid internalization of PKC-modified ErbB2. Phorbol causes sustained cytoplasmic accumulation of PKC-phosphorylated receptors, however, whereas PDGF triggers the appearance of this ErbB2 subset only briefly. Metabolic labelling and co-precipitation studies fail to implicate heterologous molecules in either the tyrosine dephosphorylation or internalization of PKC-modified ErbB2. Taken in the context of earlier juxtamembrane domain mutagenesis studies, these findings indicate that phorbol-activated PKC may desensitize growth factor receptors to extracellular ligands solely by triggering sustained receptor internalization. We submit that PKC-dependent juxtamembrane domain phosphorylation represents a physiological mechanism for shortening the duration and enhancing the specificity of growth factor signalling by promoting internalization of liganded and unliganded receptors, respectively.      

Intracranial chondroma of the occipital lobe

A case report of an intracranial chondroma is discussed with emphasis on magnetic resonance imaging.     

Follow-up of patients with previous treatment for coarctation of the thoracic aorta: comparison between contrast-enhanced MR angiography and fast spin-echo MR imaging

Regular follow-up is required in patients with previous intervention for coarctation of the aorta to detect recoarctation or aneurysm formation. In this study we describe the findings encountered on routine follow-up exams and we compare the use of contrast-enhanced 3D MR angiography (CE MRA) with fast spin-echo MRI (FSE) to study the thoracic aorta after previous intervention. In 51 consecutive patients previously treated for aortic coarctation, 74 MR studies of the thoracic aorta were performed during a 2-year period using CE MRA and FSE MRI. The thoracic aorta was evaluated for abnormalities of course, caliber, shape, and pathology of side branches. The CE MRA and FSE MRI studies were evaluated side by side by consensus of two reviewers evaluating which MR technique depicted the abnormalities of the thoracic aorta the best. Of 74 exams, six clinically important abnormalities were found: four aneurysms and two restenoses. Two small pseudoaneurysms were missed on the FSE studies. Contrast-enhanced MRA was judged to visualize aortic abnormalities better than FSE (47 of 74 MR studies) especially for the transverse aortic arch, coarctation site, left subclavian artery, and aortic arch configuration. For the ascending aorta and distal descending aorta, CE MRA and FSE performed equally well. Aortic diameters measured at four levels in the first 18 MRI studies showed no significant differences in diameter when measured by FSE or CE MRA (p = not significant). Clinically important abnormalities, such as aneurysm formation and restenosis, can be present years after treatment for aortic coarctation. In the regular follow-up of these patients, CE MRA may provide additional diagnostic information compared with FSE and should be included as part of the routine exam. Received: 3 April 2000; Revised: 5 July 2000; Accepted: 7 July 2000     

A prognostic index as diagnostic strategy in children suspected of mitochondriocytopathy

The aim of this study was to assess an optimal screening for paediatric patients suspected of mitochondriocytopathy to justify a muscle biopsy. Forty-five patients were included. Medical history, physical examination, cardiac and ophthalmologic evaluation, clinical chemical investigations, in vivo function tests, neuroimaging and a skeletal muscle biopsy were performed in all patients. The results of the biochemical muscle studies were compared with the results of the other investigations. First, parameters with a statistical relationship with the result in muscle, normal or deficient, were selected. Secondly, a prognostic index was constructed using these parameters. Five parameters were selected: age <4 years, elevated fasting lactate to pyruvate ratio, elevated thrombocyte count, elevated lactate, and elevated alanine. Each parameter was scored 0 (not present) or 1 (present). The chance of a normal biopsy with a given value of this index (sum of the scores) was calculated: logit (Pr) = alpha + beta x index; alpha: -0.8167 and beta: 0.8331. (Pr: probability of normal biopsy.) The chance of a normal biopsy with an index value of 5 is 0.03, 4 is 0.07, 3 is 0.16, 2 is 0.30, 1 is 0.50 and 0 is 0.69. This prognostic index is a valuable instrument in deciding whether the suspicion of mitochondriocytopathy is strong enough to merit a muscle biopsy.     

Multiple intracranial juvenile xanthogranulomas. Case report

The authors report on an 11-year-old boy in whom proptosis of the eye caused by a benign intraosseous xanthofibroma of the left orbital wall became clinically apparent at the age of 4 years. Two years later he developed bilateral papilledema, at which time computerized tomography and magnetic resonance studies revealed multiple enhancing intracranial lesions. The largest mass was located in the left middle fossa; other lesions were located at the tentorium cerebelli, in both lateral ventricles, near the superior sagittal sinus, and extracranially near the left jugular vein. The mass in the left middle fossa was resected and diagnosed as juvenile xanthogranuloma (JXG). Thirty months later, the patient again became symptomatic, exhibiting behavioral abnormalities and a decrease in mental powers. At that time, the two remaining lesions in both lateral ventricles had grown enough to cause trapping of the temporal horns and raised intracranial pressure. These lesions were successively resected and histopathologically confirmed to be JXGs. However, resection of the second intraventricular lesion was complicated by postoperative bilateral amaurosis, presumably caused by postdecompression optic neuropathy. According to a review of the literature, fewer than 20 patients with JXG involving the central nervous system have been reported. The patient described in this report is the first in whom multiple intracranial JXGs developed in the absence of cutaneous manifestations. Although JXGs are biologically benign lesions, the treatment of patients with multifocal and/or progressive intracranial manifestations is problematic.     

The Effects of Similarity in Sexual Excitation,Inhibition, and Mood on Sexual Arousal Problems and Sexual Satisfaction in Newlywed Couples

IntroductionDespite the importance of sexuality for romantic relationships, there has been little research attention to individual differences and dyadic variables, including couple similarity, and their association with sexual problems and satisfaction.AimThe current study examined the effects of the propensity for sexual inhibition and sexual excitation scales (SIS/SES) and the effects of different mood states on sexuality (Mood and Sexuality Questionnaire [MSQ]), at both the individual and the dyad level, on sexual arousal problems and sexual satisfaction.MethodsSimilarity in SIS/SES and MSQ was measured in a nonclinical sample of 35 newlywed couples and operationally defined as the within‐couple, z‐transformed correlations between the two partners' item responses.Main Outcome MeasuresSexual arousal problems were assessed using self‐report measures (Demographic and Sexual History Questionnaire) and focused on the past 3 months. Sexual satisfaction was assessed using the Global Measure of Sexual Satisfaction.ResultsRegression analyses revealed that greater similarity in the effects of anxiety and stress on sexuality was associated with more reported sexual arousal problems of wives. In contrast, the husbands' sexual arousal problems were related only to their own higher SIS1 scores. Higher SES scores predicted lower sexual satisfaction for both husbands and wives. Wives who reported strong positive mood effects on their sexuality indicated greater sexual satisfaction, while husbands who were more similar to their wives in the effect of positive moods on sexuality indicated greater sexual satisfaction.ConclusionsThe findings show that, above and beyond one's own sexual propensities, similarity in various aspects of sexuality predicts sexual problems (more so in women) and sexual satisfaction (in both men and women). Lykins AD, Janssen E, Newhouse S, Heiman JR, and Rafaeli E. The effects of similarity in sexual excitation, inhibition, and mood on sexual arousal problems and sexual satisfaction in newlywed couples. J Sex Med 2012;9:1360–1366.