Activation of K+ currents in cultured Schwann cells is controlled by extracellular pH

We analyzed the pH dependence of K⁺ currents recorded with the patch-clamp technique from cultured Schwann cells obtained from mouse dorsal root ganglia. Currents were activated at potentials more positive than ?50 mV which was close to the resting membrane potential. Current amplitudes were affected by a change in extracellular pH (pH_o), being increased at alkaline, and decreased at acidic pH_o. The strongest effect of a pH_o change was observed on currents activated close to the resting membrane potential suggesting a functional role for the pH sensitivity of K⁺ currents. Analysis of the time course of current activation at different pH_o values led to the conclusion that the pH-sensitivity of K⁺ currents in Schwann cells is due to changes in surface charges shifting the potential sensed by the gating process of the channel. The reversal potential of the currents was not affected by a change in pH_o. This observation and the finding that even a strong acidification to a pH_o value of 5.0 did not lead to a blockade of the fully activated channel, indicate that the pH-sensitive charges are not located in the channel pore. Under the assumption that pH_o changes in a peripheral nerve are associated with nerve activity as in the optic nerve, the pH-sensitive K⁺ channel in Schwann cells could serve to facilitate the spatial buffering of extracellular K⁺.     

Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweek mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.     

Diffusion-weighted imaging determinants for acute ischemic stroke diagnosis in the emergency room

Purpose

The aim of this study was to investigate the clinical-radiological determinants of diffusion-weighted image (DWI) abnormalities in patients with suspected acute ischemic stroke (AIS) seen at the emergency room (ER).

Methods

During the study period, 882 consecutive patients were screened at Clínica Alemana de Santiago, Chile; 786 had AIS and 711 (90.4%) were included.

Results

DWI demonstrated 87.3% sensitivity and 99.0% specificity, with a positive likelihood ratio of 79 and a negative likelihood ratio of 0.13 for the detection of AIS. In the univariate analysis, a positive DWI in AIS was associated with admission National Institute of Health Stroke Scale (NIHSS) score (OR 1.09, 95% CI 1.04–1.1%), time from symptom onset to DWI (OR 1.03, 95% CI 1.01–1.05), presence of a relevant intracranial artery occlusion (OR 3.18, 95% CI 1.75–5.76), posterior circulation ischemia (OR 0.44, 95% CI 0.28–0.7), brainstem location of the AIS (OR 0.16, 95% CI 0.093–0.27), infratentorial location of AIS (OR 0.44, 95% CI 0.28–0.70), and lacunar (OR 0.27, 95% CI 0.11–0.68) or undetermined stroke etiology (OR 0.12, 95% CI 0.3–0.31). In multivariate analysis, only admission NIHSS score (OR 1.07, 95% CI 1.01–1.13), time from symptom onset to DWI (OR 1.04, 95% CI 1.01–1.13), brainstem location (OR 0.13, 95% CI 0.051–0.37), and lacunar (OR: 0.4, 95% CI 0.21–0.78) or undetermined etiology (OR: 0.4, 95% CI 0.22–0.78) remained independently associated.

Conclusion

DWI detects AIS accurately; the positivity of these evaluations in the ER is associated only with NIHSS on admission, time to DWI, brainstem location, and AIS etiology.

     

Long-Term Complications of Treatment and Causes of Mortality After Hodgkin's Disease

The majority of newly diagnosed patients are expected to survive Hodgkin's disease because of effective therapies established during past 30 years. Long-term observations from large populations of treated patients have disclosed a variety of late effects of the disease and its therapy have contributed morbidity and excess mortality to Hodgkin's disease survivors. Secondary cancers have continued to accrue, and the risk relative to the general population has increased to 6.4 (95% confidence intervals: 5.5 to 7.3) in updated experience at Stanford University. Risks are significantly elevated for leukemia (primarily after chemotherapy regimens containing alkylating agents); non-Hodgkin's lymphoma; and tumors of the lung, breast, soft tissues, bone, stomach, pancreas, salivary gland, thyroid, and cutaneous melanoma. Early cardiovascular disease has also been observed and numerically exceeds second cancers as a cause of death in patients with early stage Hodgkin's disease (49 v 47 cases). Pulmonary dysfunction, thyroid dysfunction, infertility, psychosocial changes, gastrointestinal problems, soft-tissue changes, alterations in immunity, and risks for infection have also affected some treated patients. As these problems have been recognized, treatment approaches have been modified over the last 10 to 15 years, and early data suggest a decrease in some treatment sequellae.     

A Non-Ionic Vesicle Lipid Enhances Mastoparan-Stimulated GTPase Activity of Heterotrimeric G-Proteins

Isolated heterotrimeric G-proteins exhibit full biological activity when reconstituted into liposomes. Here, we investigated the non-ionic surfactant macrogol-260-cetylstearylether (TA 6) as an efficient vehicle for the reconstitution of G-proteins. Reconstitution efficiency of G-proteins was recorded by GTPS-binding. Their biological potency was measured as basal and mastoparan-stimulated GTPase-activity. G-proteins were fully active when associated with liposomes. On the other hand, G-proteins solubilized by TA 6 micelles or reconstituted into pure TA 6 vesicles exhibited impaired biological activity. However, vesicles containing different ratios of azolectin and non-ionic TA 6 showed about 50% higher reconstitution efficiency as compared to pure liposomes. In addition, basal and mastoparan-stimulated GTPase-activity in vesicles containing an axolectin / TA 6 ratio of 3:1 were 2.7 and 9.1 fold higher than in pure liposomes, respectively. These data emphasize that the composition of the lipid membranous environment significantly influences G-protein activity.     

Current value of double-contrast pharyngography and of computed tomography for the detection and for staging of hypopharyngeal, oropharyngeal and supraglottic tumors

In light of recent endoscopic techniques the current value of double-contrast pharyngography (DCP) and of CT for detection and staging of hypo-, oropharyngeal, and supraglottic tumors is evaluated. The DCP of 151 patients and CT obtained from 99 of these patients were retrospectively analyzed in a double-blinded manner. We used a standard protocol which comprised all relevant anatomical subregions. Results were compared with direct microlaryngoscopy (DL), indirect laryngoscopy (IL), and post-operative histopathological findings. Sensitivity and specificity of DCP was 75.0 % and 86.7 %, respectively. The DCP and IL techniques together yielded a higher sensitivity (96.7 %) than each method separately. Sensitivity and specificity of CT was 87.5 and 100 %, respectively. In 74.7 % CT provided correct staging. Subregional analysis revealed that the results of DCP and CT depend highly on the localization of the tumor. Our results indicate that DCP represents an important screening method for diagnosing hypo-, oropharyngeal, and supraglottic tumors to complete IL and DL. We show that CT is a reliable method for preoperative staging, although small superficial tumors may occasionally be missed by this method. Received: 30 November 1998; Revised: 2 March 1999; Accepted: 14 April 1999     

Two populations of glial cells from fish optic nerve/tract with distinct electrophysiological properties

Summary The electrophysiological properties of the two major glial cell types in cultures from the regenerating goldfish optic nerve/tract were studied with patch-clamp techniques. Spindle-shaped cells express myelin proteins. These oligodendrocyte-like cells possess outwardly rectifying currents, do not show glutamate activated currents and are rarely electrically coupled to neighboring cells. Cells of epitheloid morphology probably represent astrocytes. They are GFAP-positive and do not exhibit myelin proteins. These cells have glutamate activated currents, display a linear current to voltage relationship and are extensively electrically coupled thus displaying properties similar to mammalian astrocytes.