Differences in a K current in schwann cells from normal and neurofibromatosis-infected damselfish

Patch clamp techniques were used to study whole cell ionic currents in Schwann cells (SC) from a tropical marine fish, the bicolor damselfish, Pomacentrus partitus. The bicolor damselfish is affected by a disease termed damselfish neurofibromatosis (DNF), being developed as an animal model of neurofibromatosis-type 1 (NF1) in humans. NF1 affects SC, fibroblasts, and perineurial cells. The sole depolarization-activated ionic current present in cultured SC from normal fish peripheral nerve and from neurofibromas of fish with induced or spontaneously occurring DNF was an inactivating K⁺ current (K current), with a strong dependence on the Nernst potential for K⁺. This K current activated at depolarizations to -40 mV and above and inactivated during a maintained test pulse (0.2-1 s), but inactivation was significantly greater in tumored SC. Both currents were inhibited by 4-aminopyridine (K_d ? 1 mM) and by dendrotoxin (15 μM) but were insensitive to extracellular tetraethyammonium (≤ 150 mM), indicating that the whole cell currents were similar pharmacologically. The currents could be distinguished on the basis of their sensitivity to depolarized holding potential, with normal cells less sensitive. Half-inactivation of the current was -32 mV in normal cells and -38 mV in tumored cells. Inactivation curves constructed from the average normalized current for many SC were significantly different in normal and tumored cells. When the depolarized holding potential was maintained between test depolarizations, greater voltage-dependent inactivation in tumored cells was apparent. Normal cells maintained an average of 36% of peak current at a holding voltage of ?40 mV, while in tumored cells this average was 12%, a significant difference. © 1994 Wiley-Liss, Inc.     

Brevetoxin modulates neuronal sodium channels in two cell lines derived from rat brain

Single Na+ channel currents were recorded from cell-attached membrane patches from two neuronal cell lines derived from rat brain, B50 and B104, and compared before and after exposure of the cells to purified brevetoxin, PbTx-3. B50 and B104 Na+ channels usually exhibited fast activation and inactivation as is typical of TTX-sensitive Na+ channels. PbTx-3 modified channel gating in both cell lines. PbTx-3 caused (1) significant increases in the frequency of channel reopening, indicating a slowing of channel inactivation, (2) a change in the voltage dependence of the channels, promoting channel opening during steady-state voltage clamp of the membrane at voltages throughout the activation range of Na+ currents, but notably near the resting potential of these cells (-60 - -50 mV), and (3) a significant, 6.7 mV hyperpolarized shift in the threshold potential for channel opening. Na+ channel slope conductance did not change in PbTx-3-exposed B50 and B104 neurons. These effects of Pbx-3 may cause hyperexcitability as well as inhibitory effects in intact brain.     

Acidität und peptische Aktivität des Magensafts bei gesunden und Mucoviscidosis-kranken Kindern

The acid concentration and quantity, the pH and the peptic activity of the gastric juice were measured after stimulation with pentagastrin in 10 children with cystic fibrosis between the ages 2 and 12 years and in 20 healthy children of the same age group. Furthermore, the basal, maximal and peak volume outputs (BVO, MVO and PVO), the basal, maximal and peak acid outputs (BAO, MAO and PAO) and the basal, maximal and peak pepsin output (BPO, MPO and PPO) were determined. The statistical calculations were carried out with the help of partial hierarchical analysis of variance, comparison of regression curves, simple analysis of covariance and the t test. After stimulation with pentagastrin, the volume of the gastric juice, the acid quantity and the peptic activity were found to be dependent on age in healthy children as well as in children with cystic fibrosis. The maximal volume of secretion in children with cystic fibrosis is less than that of healthy children; however, the acid quantity and peptic activity show no significant difference in both groups. The volume of the gastric juice, acid quantity and peptic activity in basal and stimulated secretions, expressed in kilograms per body weight or surface area in square meters, are independent of age and show no significant difference between the two groups. In the two groups the curves for the three parameters differ significantly from one to another. There is a significant shift in the time course of the curves that deptict the acid secretion and peptic activity. Contrary to the accepted views, the acid and enzyme secretions are not closely interrelated. Based on the acidity and peptic activity, the digestive capacity of the stomach is the same for healthy children and children with cystic fibrosis. In contrast to the pancreas, there is no impairment in the exocrine function of the stomach. The gastric secretions of children with cystic fibrosis are not completely the same as in healthy children.     

Ein Fall von Lipoma multiplex symmetricum

Ohne Zusammenfassung     

CD44 is the principal mediator of hyaluronic-acid-induced melanoma cell proliferation

Interactions of the extracellular matrix component hyaluronic acid and its cellular receptors CD44 and RHAMM/IHABP have been linked to tumor progression and metastasis formation. We investigated the expression and hyaluronic-acid-dependent functions of CD44 and RHAMM/IHABP in human melanoma. Immunohistochemistry of tumor specimens at different stages of melanoma progression revealed an increased expression of CD44 and RHAMM/IHABP. High mRNA expression of CD44 was found in three highly tumorigenic melanoma cell lines compared with less tumorigenic melanoma cells or nontransformed melanocytes. RHAMM/IHABP expression was upregulated in all cell lines analyzed but not in melanocytes. In contrast to the cell surface localization of CD44, RHAMM/IHABP was detected exclusively within the cytoplasm of melanoma cells. Binding and adhesion of melanoma cells to hyaluronic acid is mainly CD44 dependent as it was inhibited to 60%--80% by an anti-CD44 monoclonal antibody whereas anti-RHAMM/IHABP sera had no effect. Culture of melanoma cells in the presence of hyaluronic acid resulted in a dose-dependent, CD44-mediated increase of melanoma cell proliferation and enhanced release of basic fibroblast growth factor and transforming growth factor beta 1. We conclude that (i) the expression of CD44 and RHAMM/IHABP is increased during melanoma progression, (ii) CD44 is the principal hyaluronic acid surface receptor on melanoma cells, and (iii) the hyaluronic-acid-induced increase of the proliferative capacity of melanoma cells is mainly dependent on CD44--hyaluronic acid interactions.     

Impact of the etiology of acute kidney injury on outcomes following liver transplantation: acute tubular necrosis versus hepatorenal syndrome

Acute kidney injury (AKI) at the time of liver transplantation (LT) has been associated with increased morbidity and mortality. In patients with potentially reversible renal dysfunction, predicting whether there will be sufficient return of native kidney function is sometimes difficult. Previous studies have focused mainly on the effect of the severity of renal dysfunction or the duration of pretransplant dialysis on posttransplant outcomes. We performed a retrospective analysis of patients who underwent LT at our center after Model for End-Stage Liver Disease-based allocation so that we could determine the impact of the etiology of AKI [acute tubular necrosis (ATN) versus hepatorenal syndrome (HRS)] on post-LT outcomes. The patients were stratified according to the severity of AKI at the time of LT as described by the Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (RIFLE) classification: risk, injury, or failure. The RIFLE failure group was further subdivided according to the etiology of AKI: HRS or ATN. The patient survival and renal outcomes 1 and 5 years after LT were significantly worse for those with ATN. At 5 years, the incidence of chronic kidney disease (stage 4 or 5) was statistically higher in the ATN group versus the HRS group (56% versus 16%, P < 0.001). A multivariate analysis revealed that the presence of ATN at the time of LT was the only variable associated with higher mortality 1 year after LT (P < 0.001). Our study is the first to demonstrate that the etiology of AKI has the greatest impact on patient and renal outcomes after LT.     

Midfacial necrotizing lesion of the nasal cavity attributable to peripheral T-cell lymphoma

The initial progression of a nonhealing ulcerative lesion in the nasopalatal region with nondiagnostic biopsy results, combined with progression of systemic symptoms, is suggestive of a PTL. Because therapy requires accurate histologic diagnosis, the clinician must be persistent to make a correct diagnosis. As the disease progresses, PTL histology matures, allowing diagnosis with immunohistochemical techniques. It is possible that earlier diagnosis will allow more timely treatment and a reduction in mortality related to this disease.