Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction.

Groups of patients with idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy or Steele-Richardson-Olszewski syndrome, matched for overall clinical disability, were compared using three computerised cognitive tests previously shown to be sensitive to frontal lobe dysfunction. On a test of planning based on the Tower of London task, all three groups were impaired, but in different ways. The groups with palsy and Parkinson's disease were slower in the measure of initial thinking time, whereas the group with multiple system atrophy was only slower in a measure of thinking time subsequent to the first move, resembling patients with frontal lobe damage. On a test of spatial working memory, each group showed deficits relative to their matched control groups, but the three groups differed in their strategy for dealing with this task. On a test of attentional set shifting, each group was again impaired, mainly at the extradimensional shifting stage, but the group with Steele-Richardson-Olszewski syndrome exhibited the greatest deficit. The results are compared with previous findings in patients with Alzheimer's disease or frontal lobe damage. It is concluded that these basal ganglia disorders share a distinctive pattern of cognitive deficits on tests of frontal lobe dysfunction, but there are differences in the exact nature of the impairments, in comparison not only with frontal lobe damage but also with one another.     

New developments in flow cytometric analyses of lymphocyte markers.

This article addresses several fundamental features of clinical flow cytometry. A practical overview of the technical and methodologic aspects of this fast-growing and increasingly important new clinical and investigative field is provided. The use of flow cytometry for the diagnosis and monitoring of various chronic lymphoproliferative diseases also is discussed. This article may serve as a useful guide to those seeking to set up or maintain a clinical flow cytometry laboratory.     

Acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system.

BACKGROUND: A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. METHODS: Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for alphavbeta3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). RESULTS: Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of alphavbeta3 (1.9-fold, p < 0.001), tissue factor (1.8-fold, p < 0.001), and EMMPRIN (1.5-fold, p < 0.001). All patients in the AVR group received plasmapheresis; 11 of 14 patients had evidence of ischemic necrosis on biopsy specimens, and 3 of 14 patients experienced hemodynamic compromise and graft dysfunction and died within 3 weeks of transplant. Another patient died at 10 months after transplant. CONCLUSIONS: Acute vascular rejection is associated with up-regulation of alphavbeta3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.     

The spread of AIDS

At a panel on Acquired Immune Deficiency Syndrome (AIDS) and the 3rd world in January 1988, experts focused on the profound problems generated by the AIDS pandemic. The World Health Organization (WHO) estimates that 3-5 million people in at least 127 countries now suffer from AIDS and that this figure will reach 10-30 million by 2000. The disease represents a highly debilitating force, both socially and economically, even in nations able to afford the approximately $6000/patient cost per year of treating AIDS patients. Panelists suggested that this could prove devastating for the poorer nations. WHO's AIDS program, launched in February 1987, focuses on the development and support of national AIDS control programs. It now operates in 93 countries, and 34 more countries are scheduled to join in 1988. WHO has assisted another 58 countries with shortterm AIDS action plans. The US Agency for International Development has developed a 2-pronged strategy for curbing the pandemic with prevention-emphasis programs operating under WHO.     

Post-Traumatic Headache with Scintillating Scotoma Treated with Phenytoin (Dilantin)

A post-traumatic headache patient was experiencing "flashing lights" in her visual field that correlated with sharp waves on the EEG. Phenytoin markedly improved the symptoms. The value of the EEG in post-traumatic headaches is reviewed. The use of phenytoin in headache syndromes and in prevention of post-traumatic epilepsy is discussed.     

Topography of glycosylation in yeast: characterization of GDPmannose transport and lumenal guanosine diphosphatase activities in Golgi-like vesicles.

"Outer-chain" addition of mannose residues to yeast glycoproteins occurs in the Golgi compartment of the cell. Essential steps in this process are thought to include transport of GDPmannose from the cytoplasm into the lumen of Golgi vesicles, transfer of mannose to glycoprotein acceptors, hydrolysis of the resulting GDP to GMP, and return of GMP and inorganic phosphate to the cytoplasm. We report detection and characterization of a GDPmannose transport activity and a GDPase by yeast vesicles. The active transport of GDPmannose as well as the GDPase and another presumed Golgi enzyme, alpha 1,2-mannosyltransferase, are concentrated in a subcellular fraction that can be partially separated, by velocity sucrose gradient centrifugation, from a fraction enriched in an endoplasmic reticulum marker enzyme.     

Clinically established hemostatic scaffold (tissue fleece) as biomatrix in tissue- and organ-engineering research

Various types of three-dimensional matrices have been used as basic scaffolds in myocardial tissue engineering. Many of those are limited by insufficient mechanical function, availability, or biocompatibility. We present a clinically established collagen scaffold for the development of bioartificial myocardial tissue. Neonatal rat cardiomyocytes were seeded into Tissue Fleece (Baxter Deutschland, Heidelberg, Germany). Histological and ultrastructural examinations were performed by DAPI and DiOC(18) staining and electron microscopy, respectively. Force measurements from the spontaneously beating construct were obtained. The constructs were stimulated with agents such as adrenalin and calcium, and by stretching. Passive stretch curves were obtained. Spontaneous contractions of solid bioartificial myocardial tissue (BMT), 20 x 15 x 2 mm, resulted. Contractions continued to week 12 (40% of BMTs) in culture. Histology revealed intercellular and also cell-fibril junctions. Elasticity was similar to that of native rat myocardium. Contractile force increased after topical administration of Ca(2+) and adrenaline. Stretch led to the highest levels of contractile force. In summary, bioartificial myocardial tissue with significant in vitro longevity, spontaneous contractility, and homogeneous cell distribution was produced using Tissue Fleece. Tissue Fleece constitutes an effective scaffold to engineer solid organ structures, which could be used for repair of congenital defects or replacement of diseased tissue.