Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin.

One of the consequences of increased intracellular calcium in response to a variety of physiological stimuli is the calcium activation of cytosolic proteases. Unlike lysosomal proteases with broad specificity, these calcium-activated neutral proteases show limited proteolysis of a restricted set of substrate proteins suggesting they may play a regulatory role in cellular physiology. In this study we show that the neural cell adhesion molecules NCAM-180 and N-cadherin are substrates for such endogenous calcium-activated neutral proteases. In contrast, a third neural cell adhesion molecule G4/L1 was not susceptible to calcium-activated proteolysis. The threshold for activation of NCAM and N-cadherin proteolysis is in the micromolar range of calcium suggesting that NCAM and N-cadherin are substrates for a mu-type calpain (calpain I). The site recognized by this protease is within intracellular domains of NCAM-180 and N-cadherin which are important for their interaction with cytoskeletal components. These results suggest that calcium-activated proteolysis at these sites in vivo could disrupt the linkage between extracellular ligand binding to these adhesion molecules and the normal intracellular effectors of such extracellular binding events.     

A new method for producing temporary complete cerebral ischemia in rats

A new model of temporary complete cerebral ischemia was developed and tested in 64 rats. With use of microsurgical techniques, both pterygopalatine and external carotid arteries were occluded and the basilar artery was coagulated to reduce potential collateral CBF during ischemia. After this preliminary five-vessel occlusion, temporary global ischemia was induced by occluding the common carotid arteries (CCAs) with microclips. To validate the method, CBF was measured autoradiographically in 24 anatomical regions at death after 5 min of ischemia or after 15 min of ischemia followed by 5 min of reperfusion. Mean arterial blood pressure and arterial blood gases remained stable under controlled endotracheal ventilation and anesthesia (halothane, 70% N2O, and 30% O2) throughout the CBF experiments, except for a 10-15% increase in mean arterial blood pressure for 1-5 min after bilateral CCA occlusion. After the initial five-vessel occlusion, the EEG did not change, and local CBF levels were comparable to those in anesthetized non-surgical controls. When the CCAs were occluded, the EEG flattened rapidly; after 5 min of ischemia, autoradiography showed no detectable blood flow in the forebrain and cerebellum. The local CBF levels measured after 15 min of temporary global ischemia and 5 min of reperfusion demonstrated relatively homogeneous postischemic hyperperfusion; only two of eight rats had several 1- to 3-mm areas of no-reflow. Survival studies showed increasing motor impairment after 10, 15, 30, and 60 min of temporary CCA occlusion. Ischemic neuronal damage was observed histologically in the hippocampus and basal ganglia 24 h after 10 min of temporary ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Four primary malignant tumors, including malignant melanoma and malignant lymphoma, in the same adult patient

We report an 80-year-old Japanese male with four primary malignant tumors: malignant melanoma, prostatic cancer, malignant lymphoma, and renal cell carcinoma, which occurred in that respective order. The combination of malignant melanoma and malignant lymphoma is rare. The patient was treated with BCG after an operation for malignant melanoma. He was also treated with cobalt 60 irradiation after an operation for prostatic cancer. We also discuss other reports of multiple malignant tumors and suggest some possible causes of this patient's primary malignant tumors.     

Central venous catheter-related Rhodotorula rubra fungemia

With the increased use of indwelling central venous catheters, increasing numbers of cases of Rhodotorula fungemia have been observed in patients with neoplasia and neutropenia. In most patients with catheter-related Rhodotorula fungemia, the condition has been treated with broadspectrum antibiotics. We report two cases of central venous catheter-related Rhodotorula rubra fungemia that occurred in patients with acute myeloblastic leukemia. Both patients were in a state of neutropenia. One patient was treated with amphotericin B and his central venous catheter was removed, but he died of Klebsiella pneumoniae bacteremia. The other patient was treated with amphotericin B and discharged, with a central venous catheter, after recovery from neutropenia. Although the management of catheter-related Rhodotorula fungemia infections remains controversial, resolution of the underlying disease is more important than catheter removal for recovery from Rhodotorula rubra fungemia. Received: August 22, 2001 / Accepted: October 8, 2001     

Catechol oxidation by peroxidase-positive astrocytes in primary culture: an electron spin resonance study.

In rodents, chronic estrogenization has been shown to induce degeneration of dendrites and myelin figures in the hypothalamic arcuate nucleus adjacent to peroxidase-positive astrocyte processes. Because in this brain region estradiol is metabolized to 2-hydroxyestradiol (catecholestrogen), we hypothesized that the latter may be oxidized by the astrocytic peroxidase activity to cytotoxic ortho-semiquinones as occurs in peripheral tissues. Cysteamine induces nonenzymatic peroxidase activity in cultured astroglia identical to that observed in vivo. Using electron spin resonance, we demonstrate robust peroxidase-catalyzed oxidation of 2-hydroxyestradiol and dopamine by cysteamine-pretreated astrocyte cultures relative to untreated controls. These results implicate the peroxidase-positive astrocytes in the pathogenesis of estradiol-related hypothalamic damage, parkinsonism, and other free-radical-related neurologic disorders.     

Clinical efficacy of clarithromycin in the field of pediatrics

A new macrolide antibiotic, clarithromycin (TE-031, A-56268), was studied for its clinical efficacy in the field of pediatrics. Patients treated were infants and children ranging from 2 months to 11 years old suffering from acute bronchitis in 5 cases, acute tonsillitis in 2 cases, Mycoplasma pneumonia in 2 cases, pertussis in 6 cases, scarlatina in 1 case and acute enteritis in 2 cases, a total of 18 cases. TE-031 was administered 19.7-43.5 mg/kg in daily doses and lengths of treatment ranged from 4 to 19 days. As regards to its clinical efficacy, good or excellent results were obtained in all cases: excellent in 11 cases and good in 7 cases. No clinical side effects nor abnormal laboratory test values obviously attributable to TE-031 were observed.