Cholecystokinin in anxiety

Cholecystokinin (CCK) plays an important role in both the alimentary tract and the central nervous system (CNS). At present it seems to be the most abundant neuropeptide in the CNS. This paper reviews the CCK neuronal system and its interactions with gamma-aminobutyric acid (GABA) and serotonin (5-hydroxytryptamine; 5-HT). In addition, its putative role in anxiety will be discussed on the basis of animal data and studies in healthy volunteers and panic disorder patients. According to these investigations, the CCK4 challenge test fulfills most criteria for an ideal panicogenic agent and evidence has been found that CCKB receptor antagonists might possess anxiolytic properties in man.     

Chronic obstructive pulmonary disease: role of bronchiolar mast cells and macrophages

Chronic obstructive pulmonary disease (COPD) is considered to be caused in part by smoking-induced inflammation, but it is unknown which inflammatory cells within the small airways are associated with the obstruction. We investigated the inflammatory infiltrate in the small airways of 16 current or ex-smokers with COPD (FEV1 < or = 75% predicted) and 15 without COPD (FEV1 > or = 85% predicted) in pneumectomy specimens that were removed for lung cancer. Mast cells, macrophages, neutrophils, eosinophils, T cells, and B cells were identified using immunohistochemistry on formalin-fixed, paraffin-embedded specimens. These cells were quantified in the epithelium and the remainder of the airway wall. The number of mast cells and macrophages in the epithelium, but not in the remainder of the airway wall, was significantly increased in patients with COPD. Neutrophil and T cell numbers did not differ between the groups. Only few B cells and eosinophils were present in both groups. Smoking history, perioperative steroid usage, tumor localization, or reversibility in the FEV1 to salbutamol could not account for the observed differences. We conclude that the number of epithelial mast cells and macrophages is increased in the bronchioli in smokers with airflow limitation, suggesting a role in development of COPD.     

Atrophy and degeneration of peptidergic neurons and cessation of egg laying in the aging pond snail Lymnaea stagnalis

The morphology of the neuroendocrine caudodorsal cells (CDCs), which are involved in the regulation of female reproduction in the pond snail Lymnaea stagnalis, was studied in young (200 to 234 days of age) and old (400 to 500 days) animals. Lucifer Yellow fills of ventral CDCs showed that in young animals ventral CDCs branch ipsilaterally as well as contralaterally in the cerebral commissure. In old animals these branches were reduced at different degrees and in some cases even lacking completely, leaving only an axon crossing the commissure. Immunocytochemical stainings with antibodies against CDC peptides (CDCH-I and alpha CDCP) corroborated the finding that ventral CDCs degenerate. Among the other types of CDCs (dorsal, lateral), degeneration was found as well. The immunocytochemical findings showed that in old animals the axon terminals of the CDCs were strongly stained, indicating that they are packed with secretory vesicles containing peptides. It was also found that these darkly stained, peptide-containing axon terminals protruded into the perineurium. These findings suggest that accumulation of peptides in the terminals of the CDCs of old animals may be due to the impaired release. The relationship between atrophy and degeneration of CDCs and cessation of egg-laying activity in Lymnaea is discussed.     

A note on force plane diagrams for elastic and elastic-plastically stressed thick-walled cylinders

Force plane diagrams, drawn from force equilibrium considerations, have been obtained for elastic, elastic-plastic and plastically stressed thick-walled cylinders subjected to internal pressure deforming under conditions of plane strain. The force on any plane at right angles to the plane of deformation can easily be found by using the diagrams. Force plane diagrams for non-fully plastic cases have not previously been given.     

Low-loss phased-array based 4-channel wavelength demultiplexerintegrated with photodetectors

A 4-channel phased-array wavelength division demultiplexer with 1.8 nm channel spacing at 1.54 μm has been monolithically integrated with photodetectors in InP/InGaAsP. On chip losses are 3.5 to 4.5 dB. These are the lowest losses reported so far for demultiplexers monolithically integrated with photodetectors. Nearest neighbor crosstalk ranges from -12 to -21 dB     

Recombinant human acid alpha-glucosidase: high level production in mouse milk, biochemical characteristics, correction of enzyme deficiency in GSDII KO mice

Glycogen storage disease type II (GSDII) is caused by lysosomal acid alpha-glucosidase deficiency. Patients have a rapidly fatal or slowly progressive impairment of muscle function. Enzyme replacement therapy is under investigation. For large-scale, cost-effective production of recombinant human acid alpha-glucosidase in the milk of transgenic animals, we have fused the human acid alpha-glucosidase gene to 6.3 kb of the bovine alphaS1-casein gene promoter and have tested the performance of this transgene in mice. The highest production level reached was 2 mg/ml. The major fraction of the purified recombinant enzyme has a molecular mass of 110 kDa and resembles the natural acid alpha-glucosidase precursor from human urine and the recombinant precursor secreted by CHO cells, with respect to pH optimum, Km, Vmax, N-terminal amino acid sequence and glycosylation pattern. The therapeutic potential of the recombinant enzyme produced in milk is demonstrated in vitro and in vivo. The precursor is taken up in a mannose 6-phosphate receptor-dependent manner by cultured fibroblasts, is converted to mature enzyme of 76 kDa and depletes the glycogen deposit in fibroblasts of patients. When injected intravenously, the milk enzyme corrects the acid alpha-glucosidase deficiency in heart and skeletal muscle of GSDII knockout mice.     

Mechanism and Kinetics of some Reactions on Silica-Alumina Catalysts

The dehydration of alcohol when its vapor is led over alumina, or some other heterogeneously acting catalysts, is already known from the end of the eighteenth century.     

High-temperature liquid chromatography coupled on-line to a continuous-flow biochemical screening assay with electrospray ionization mass spectrometric detection

The potential of high-temperature liquid chromatography (HTLC) was investigated in an on-line combination with a screening system for bioactive compounds against the enzyme cathepsin B. Samples were separated by HTLC and subsequently analyzed by an on-line continuous-flow enzymatic assay. Detection was performed by electrospray ionization mass spectrometry, revealing both the bioactivity and the molecular mass of the bioactive compounds. Compared to conventional reversed-phase liquid chromatography, the amount of methanol necessary for separation could be decreased to only 10%, which improved the compatibility of LC with a biochemical assay. Sufficient preheating of the mobile phase prior to the separation and postcolumn cooling to prevent deactivation of the enzyme, even at column temperatures as high as 208 degrees C, was achieved as indicated by the reliable peak shapes obtained. The sensitivity was comparable with previously described systems operating at ambient temperatures as similar IC50 values were obtained. Exposing the inhibitors to high temperatures did not lead to thermal decomposition. The separation of inhibitors and the subsequent biochemical assay was performed either isothermally at various temperatures or by applying various temperature gradients as well as at various flow rates. The results obtained clearly show the compatibility of HTLC with an enzymatic screening assay.