ABSTRACT
Gorlin syndrome (MIM 109,400), a cancer predisposition syndrome related to a constitutional pathogenic variation (PV) of a gene in the Sonic Hedgehog pathway (PTCH1 or SUFU), is associated with a broad spectrum of benign and malignant tumors. Basal cell carcinomas (BCC), odontogenic keratocysts and medulloblastomas are the main tumor types encountered, but meningiomas, ovarian or cardiac fibromas and sarcomas have also been described. The clinical features and tumor risks are different depending on the causative gene. Due to the rarity of this condition, there is little data on phenotype-genotype correlations. This report summarizes genotype-based recommendations for screening patients with PTCH1 and SUFU-related Gorlin syndrome, discussed during a workshop of the Host Genome Working Group of the European branch of the International Society of Pediatric Oncology (SIOPE HGWG) held in January 2020. In order to allow early detection of BCC, dermatologic examination should start at age 10 in PTCH1, and at age 20 in SUFU PV carriers. Odontogenic keratocyst screening, based on odontologic examination, should begin at age 2 with annual orthopantogram beginning around age 8 for PTCH1 PV carriers only. For medulloblastomas, repeated brain MRI from birth to 5 years should be proposed for SUFU PV carriers only. Brain MRI for meningiomas and pelvic ultrasound for ovarian fibromas should be offered to both PTCH1 and SUFU PV carriers. Follow-up of patients treated with radiotherapy should be prolonged and thorough because of the risk of secondary malignancies. Prospective evaluation of evidence of the effectiveness of these surveillance recommendations is required.
Subject(s)
Basal Cell Nevus Syndrome , Cerebellar Neoplasms , Skin Neoplasms , Basal Cell Nevus Syndrome/diagnosis , Basal Cell Nevus Syndrome/genetics , Cerebellar Neoplasms/diagnosis , Cerebellar Neoplasms/genetics , Child , Child, Preschool , Hedgehog Proteins/genetics , Humans , Patched-1 Receptor/genetics , Repressor Proteins/genetics , Young AdultABSTRACT
The loading and loss kinetics of cellular 45Ca were studied in rat liver cells. The data are described by a three compartment system. Six arrangements of the exchange pathways of these pools are presented. Taking into account the Ca stocking properties of cell organels, two models may be emphasized.
Subject(s)
Calcium/metabolism , Liver/metabolism , Animals , Biological Transport , In Vitro Techniques , Kinetics , Models, Biological , RatsSubject(s)
Liver/metabolism , Potassium/metabolism , Animals , Biological Transport , Carbon Radioisotopes , Cell Membrane/drug effects , Cell Membrane/metabolism , Chlorides/metabolism , Chlorine , Intracellular Fluid/metabolism , Inulin/metabolism , Kinetics , Liver/cytology , Liver/drug effects , Mathematics , Osmolar Concentration , Perfusion , Permeability , Potassium/pharmacology , Potassium Isotopes , Radioisotopes , Rats , Sodium/metabolism , Sodium Isotopes , Water/metabolismABSTRACT
1. The ouabain-sensitive component of Na efflux and K influx amount to 58 and 72% respectively. Taking into account also (a) the diffusional passive fluxes of Na (5%) and K (13%), as estimated by Ussing's equation and (b) the ouabain-insensitive Na-Na exchange (28%), 85% (K) and 90% (Na) of the measured total fluxes can be accounted for.2. Na efflux is diminished when K is partially or totally removed from the medium. This effect is reversible, indicating probably activation of the Na pump by external K.3. The coupling ratio of Na and K ouabain-sensitive fluxes is equal to 1.58, suggesting that three Na ions are removed from and two K ions are carried into the cell in one cycle of the pump. Hence, in liver cell membranes, the Na pump must be electrogenic.4. A tenfold decrease in [Cl](o) by substitution with an impermeant anion results in a membrane hyperpolarization and a decrease in [Cl](i). Cl loss from the liver is compensated by an equivalent loss of intracellular K to preserve electroneutrality.5. The measurement of passive fluxes indicates that Cl removal from the perfusing solutions increases P(K) but does not alter P(Na).6. Addition of ouabain brings about a depolarization which is three times greater in low-Cl solutions (21.9 mV) than in normal-Cl solutions (6.8 mV).7. It is concluded that hyperpolarization which develops when Cl ions are removed can be accounted for entirely by (a) the increase in P(K), (b) the increase of the contribution of the electrogenic pump to membrane potential.
