The tyrosine kinase regulator Cbl enhances the ubiquitination and degradation of the platelet-derived growth factor receptor alpha

The Cbl protooncogene product has emerged as a negative regulator of receptor and nonreceptor tyrosine kinases. We recently demonstrated that oncogenic Cbl mutants upregulate the endogenous tyrosine kinase signaling machinery when expressed in the NIH 3T3 cells, and identified the platelet-derived growth factor receptor-alpha (PDGFRalpha) as one of the tyrosine kinases targeted by these oncogenes. These findings suggested a role for the normal Cbl protein in negative regulation of the PDGFRalpha. However, the mechanism of such negative regulation remained to be determined. Here we show that overexpression of the wild-type Cbl enhances the ligand-induced ubiquitination of the PDGFRalpha. Concomitantly, the PDGFRalpha in Cbl-overexpressing cells undergoes a faster ligand-induced degradation compared with that in the control cells. These results identify a role for Cbl in the regulation of ligand-induced ubiquitination and degradation of receptor tyrosine kinases and suggest one potential mechanism for evolutionarily conserved negative regulatory influence of Cbl on tyrosine kinases.     

Fragile ''X'' syndrome. A case study

Aim of this paper is to assess the validity of bone scanning for radiation therapy treatment planning in the skeletal system. Radiation therapy treatment planning in the skeletal system is based on plain film radiographs and bone scanning. Between January 1, 1993 and June 30, 1994, 228 patients were irradiated due to malignancies in the skeletal system. Included were bone metastases, lymphomas, sarcomas and bone invasion of neuroblastoma. The morphological display of the plain film radiographs and the bone scintigraphies were compared and modifications of the target volume due to the scan findings quantified. In 17 of 228 patients (7.5%) the target volume was modified by at least 2 cm due to tumor invasion depicted by radionuclide scanning only. Bone scintigraphy enables a sensitive display of bony invasion in skeletal malignancies. Because of a scan induced alteration of the target volume in 7.5% of the cases, bone scanning cannot be abandoned in RT treatment planning.     

Clinical study on effect of xinjikang capsule in reversing left ventricular hypertrophy

OBJECTIVE: To demonstrate the presence of endothelin-1 (ET-1), atrial natriuretic peptide (ANP) in peritoneal fluid of women and their effects on pathogenesis of pelvic venous congestion syndrome after sterilization (PVCSS). METHODS: This randomized controlled study determined the concentrations of ET-1 and ANP in both peritoneal fluid and plasma, counts of macrophage in peritoneal fluid and volumes of peritoneal fluid in 21 cases of PVCSS. 12 normal women after sterilization and 11 normal women as control in early follicular phase by radioimmunoassay. RESULTS: concentrations of ET-1, ratio of ET-1/ANP and counts of macrophage in peritoneal fluid with PVCSS were lower than those in control (P < 0.005, P < 0.001, P < 0.001) and all had significant negative correlation with scores quantifying the severity of PVCSS (P < 0.05), but volumes of peritoneal fluid in PVCSS were larger than that in control (P < 0.001); counts of macrophage in peritoneal fluid had significant positive correlation with the concentrations of ET-1 of peritoneal fluid in all the three groups (P < 0.05); plasma concentrations of ET-1 and ANP didn't show any significant differences among the three groups (P > 0.05). CONCLUSIONS: ET-1 was present in peritoneal fluid of normal women. Lower concentrations of ET-1 and (or) lower ratio of ET-1/ANP in peritoneal fluid contributed to the pathogenesis of PVCSS.     

Does hysteroscopy improve upon the sensitivity of dilatation and curettage in the diagnosis of endometrial hyperplasia or carcinoma?

We report the occurrence of a relapsing, severe predominantly motor neuropathy in a 75-year-old man with an IGM-K M-protein binding to gangliosides GM2, GM3, GM4, GD1a, GT1b and LM1. Motor nerve conduction velocities were slowed with conduction block. A superficial peroneal nerve biopsy specimen revealed segmental demyelination and remyelination. The patient improved after repeated plasma exchanges, and the antibody titer decreased in association with clinical recovery. This IgM M-protein has a unique, previously unreported binding specificity for terminal NeuAcalpha2-3Galbeta- moiety in common to all gangliosides bound by the antibody except GM2. M-proteins with this affinity may be involved in the pathogenesis of this and other cases of motor-dominant demyelinating neuropathy.     

Iontophoretically applied corticosteroids do not affect the firing of hippocampal neurons

In view of the possible role of the hippocampus in the neuroendocrine regulation of ACTH secretion, experiments were conducted in rats and cats in which cortisol (C) and corticosterone (CS) were applied by iontophoresis and pressure microinjection while recording from single identified pyramidal cells in the dorsal hippocampus, using multi-barrelled microelectrodes. None of the more than 500 cells tested responded with a significant change in firing rate. The possible relation of these findings to neuroendocrine regulation of ACTH secretion is discussed.     

Low levels of beta hexosaminidase A in healthy individuals with apparent deficiency of this enzyme

The common denominator of the different meanings of dizziness is a disturbance of spatio-postural orientation, which indicates an imminent danger of fall. H?henschwindel (fear of hights) with grasping and holding in the primate is instinctive behavior caused by a visual cliff or sudden dizziness. Because of the many possible meanings of dizziness, the case history is important for differential diagnosis. Vertiginous and non-vertiginous dizziness, black out and unsteady gait without vertigo should be distinguished. In addition, the duration and time course of the attack, releasing mechanisms and accompanying symptoms of dizziness should be explored. In recurrent dizziness without hearing loss, vestibular, vascular, cardial and epileptic disorders should be considered as well as intoxication, cerebral tumor, cerebellar hemangioblastoma, multiple sclerosis, neurosis and psychosis. Epileptic dizziness occurs not only in the prodromal stage of grand mal attacks and in temporal lobe epilepsy, but also in petit mal absences of short duration (less than 5 s) in which the blurring of consciousness is not apparent; absences of short duration are easily overlooked in childhood. Besides the objective history obtained from the patient's relatives, EEG-recording when falling asleep in the morning after one night of sleep deprivation are the best means for the diagnosis of epilepsia. Spontaneous nystagmus after complete exclusion of visual fixation is a physiological phenomenon. For differential diagnosis between physiological and pathological spontaneous nystagmus, Frenzel's spectacles in the dark room are indispensable. The distinction of spontaneous nystagmus in the narrower sense, gaze nystagmus and fixation nystagmus is discussed. The diagnostic importance of the direction of nystagmus is mentioned. Jerking nystagmus may be congenital. Pendular nystagmus may be acquired. Therefore, additional criteria for the differential diagnosis between congenital and acquired nystagmus are necessary.