Spatial gradients of cytosolic calcium concentration in neurones during paradoxical activation by calcium

PURPOSE: To assess long-term survival following cladribine salvage treatment for previously treated patients with chronic lymphocytic leukemia. PATIENTS AND METHODS: Fifty-two patients aged 39-84 years with previously treated CLL received cladribine 0.12 mg/kg/day in 2-hour infusions for 5 days in monthly courses. Two-thirds were refractory to previous therapy, and 8 had prior fludarabine. RESULTS: Sixteen (31%) patients achieved complete response (CR) and 14 (27%) partial remission (PR) according to consensus criteria. Response correlated with clinical stage, number of previous treatment regimes, blood lymphocyte count, and lymphocyte halflife following the first cladribine course. Toxicity included pneumonia (n = 9), herpes zoster (n = 7), and septicemia (n = 2). Four patients in CR underwent high-dose chemotherapy with autologous blood stem cell support, and 2 remain in CR 48 and 60 months from start of cladribine, and 2 had relapse at 42 and 48 months, respectively. Median progression-free survival (Kaplan-Meier analysis) for CR patients was 23 months from start of cladribine treatment, and for PR patients 16 months. The projected overall survival was 80% at 3 years for CR patients, and the median survival 28 months for PR patients and 4 months for non-responding patients. CONCLUSIONS: Our previous finding of durable CRs from cladribine in advanced CLL is thus confirmed in a larger patient material, and follow-up indicate that long-term survival may be achieved.     

Growth hormone axis in cushing''s syndrome

This article reviews some recent studies on alcohol preference, dependence, metabolism and pharmacokinetics which were mainly carried out in our department. The inbred strains of mice with genetically different alcohol drinking behavior and alcohol animal model treated with the neurotoxins, 6-hydroxydopamine and 5,7-dihydroxytryptamine, are useful for a behavioral and pharmacological approach to evaluate the contribution of specific neural systems to alcohol, drug dependence mechanism and alcohol drinking behavior. The relations between alcohol preference and some physiological conditions are reviewed. On the drug-alcohol interaction, some drugs containing the chemical group = CHONO2, antimony and methamphetamine are addressed. This article also deals with recent topics in the pharmacokinetics and pharmacodynamics of alcohol. The dose-dependency of the alcohol elimination rate, the first-pass metabolism during alcohol drinking, and the pharmacodynamic model for describing pulse rate reaction to plasma acetaldehyde are discussed.     

Laminin directs growth cone navigation via two temporally and functionally distinct calcium signals

During development, growth cones navigate to their targets via numerous interactions with molecular guidance cues, yet the mechanisms of how growth cones translate guidance information into navigational decisions are poorly understood. We have examined the role of intracellular Ca2+ in laminin (LN)-mediated growth cone navigation in vitro, using chick dorsal root ganglion neurons. Subsequent to contacting LN-coated beads with filopodia, growth cones displayed a series of stereotypic changes in behavior, including turning toward LN-coated beads and a phase of increased rates of outgrowth after a pause at LN-coated beads. A pharmacological approach indicated that LN-mediated growth cone turning required an influx of extracellular Ca2+, likely in filopodia with LN contact, and activation of calmodulin (CaM). Surprisingly, fluorescent Ca2+ imaging revealed no LN-induced rise in intracellular Ca2+ in filopodia attached to their parent growth cone. However, isolation of filopodia by laser-assisted transection unmasked a rapid, LN-specific rise in intracellular Ca2+ (+73 +/- 11 nM). Additionally, a second, sustained rise in intracellular Ca2+ (+62 +/- 8 nM) occurred in growth cones, with a distinct delay 28 +/- 3 min after growth cone filopodia contacted LN-coated beads. This delayed, sustained Ca2+ signal paralleled the phase of increased rates of outgrowth, and both events were sensitive to the inhibition of Ca2+/CaM-dependent protein kinase II (CaM-kinase II) with 2 microM KN-62. We propose that LN-mediated growth cone guidance can be attributed, in part, to two temporally and functionally distinct Ca2+ signals linked by a signaling cascade composed of CaM and CaM-kinase II.     

Cytotoxic Rhodium(III) and Iridium(III) Polypyridyl Complexes: Structure–Activity Relationships,Antileukemic Activity,and Apoptosis Induction

Whereas the cytostatic agents mer‐[RhX₃(DMSO)(pp)] (X=Cl, Br; pp=phen, dpq) are considerably more potent than their facial isomers, this order is reversed for the analogous kinetically more inert Ir^III polypyridyl complexes. The complexes induce specific apoptotic cell death in leukemia and lymphoma cells via the intrinsic mitochondrial pathway and cause negligible necrotic damage.

     

Deforming arthropathy or lupus and rhupus hands in systemic lupus erythematosus

OBJECTIVE: Although deforming arthropathy in systemic lupus erythematosus (SLE) is characterised by a number of manifestations, definitive criteria for the different forms have not yet been established. To define deforming arthropathy and its different types a study was undertaken of 176 SLE patients. METHODS: Using as criterion any deviation from any of the metacarpus finger axes 17 patients (16 women, one man) were identified with clinical deforming arthropathy. These patients were evaluated according to a standardised protocol that covered all known characteristics of deforming arthropathy. By means of "Jaccoud's arthropathy index" three different forms were identified. RESULTS: Three patients had an erosive form of deforming arthropathy (or rhupus hand) such as those seen in frank rheumatoid arthritis (RA), eight patients were identified as having Jaccoud's arthropathy (or lupus hand), and the remaining six patients had mild deforming arthropathy. Jaccoud's arthropathy is characterised by severe deformation of the hands (ulnar deviation, swan neck deformities, and Z deformity of the thumb) and feet with multiple non-erosive subluxations, mild aching and little or no evidence of synovitis. All patients, but one, fulfilled just four criteria of the ACR classification and joint symptoms were always found to precede the diagnosis of SLE. Furthermore a remarkable association of Jaccoud's arthropathy with fetal loss, thrombosis--both venous and arterial--and the presence of antiphospholipid antibodies was found. CONCLUSIONS: These data suggest that Jaccoud's arthropathy represents a subset of SLE. Subdivision of deforming arthropathy into several clinical forms can facilitate the clinical management of this disorder.     

Gekoppelte Modellierung geohydraulischer und limnophysikalischer Vorg?nge in Tagebaurestseen und ihrer Umgebung

Die beiden Restl?cher 1a und 1b des ehemaligen Braunkohlentagebaus Merseburg-Ost in Sachsen-Anhalt werden nach einer Periode des natürlichen Wasseransteiges zur Zeit mit Wasser aus der Wei?en Elster geflutet. Die langfristig sich einstellende Beschaffenheit der so entstehenden Seen, insbesondere der Grad der Versalzung durch salinare Tiefenw?sser und das Verhalten der entstandenen Monimolimnien (hochsalinare Schichten am Seegrund), mu? eingesch?tzt werden. Um der Wechselwirkung zwischen Restsee und geologischer Umgebung Rechnung zu tragen, erfolgte dazu eine Kopplung zwischen einem hydrogeologischen 3D-Modell der dichteabh?ngigen Str?mung zur Vorhersage der Grundwasserzu- und abflüsse und einem limnophysikalischen Bilanzmodell hoher vertikaler Aufl?sung zur Vorhersage der Vorg?nge innerhalb der Seen. Die Ergebnisse einer gekoppelten Langzeitrechnung über 100 Jahre werden vorgestellt, und das unterschiedliche Verhalten der Seen wird mit den unterschiedlichen Grundwasserzuflüssen begründet.     

Functional compartmentalization of the neuronal growth cone: determining calcium's place in signaling cascades

The growth cone is generally regarded as the basic unit of neuronal organization concerned with development of connections within the nervous system. The discussion below illustrates that the growth cone itself can be subdivided into distinct units of organization. It is this functional compartmentalization which enables the growth cone to read the molecular terrain it traverses and to convert this information into precise motor events. Our discussion will focus on the flow of information from the environment to the growth cone. In particular, we will follow signaling events from their remote processing within filopodia to the biological equivalent of a central processing unit in the core of the growth cone.     

Analysis of a network of electrically coupled neurons producing rhythmic activity in the snail Helisoma trivolvis

Root tip mitosis in both Vinca rosea and the chosen control Lepidium sativum is susceptible to the effects of colchicine at and above 5X10(-4)M.--Root tip mitosis in L. sativum is susceptible to the effects of vinblastine at concentrations equal to and greater than 10(-4)M, while root tip mitosis in V. rosea, the plant which is the source of vinblastine, is unaffected by exogenously-applied VBL at concentrations up to and including 10(-2)M.--The possible mechanisms by which the resistance of V. rosea to vinblastine might be conferred are discussed.     

Long-term course of tear gland function in patients with keratoconjunctivitis sicca and Sj?gren''s syndrome

The reliability and validity of a Confidence of Dental Hygienist in Child Management Scale were examined. Forty-eight dental hygiene students, nine dental staff, and thirty-one dentists were subjects for the reliability and validity scale. The acceptable level of the reliability on the Scale was shown by internal consistency and stability. The confidence scores of the clinician's group were significantly higher than the confidence scores of the students. The reliability and validity of the Confidence Scale were established. Next, we evaluated the effect of behavioral science training, using videotape feedback and role playing on twelve dental hygiene students. Six students received the training, the other six students, the controls, had no training. The confidence scores of the training group were significantly higher than those of the control group, demonstrating that the training was effective for dental hygiene students.