The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats

The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after i.v. administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P < 0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P < 0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity.     

Lysosomal enzyme and inhibitor levels in the human trabecular meshwork

PURPOSE: To examine in the human trabecular meshwork lysosomal enzymes and one inhibitor of serine proteases that actively participate in the degradation of macromolecules into low molecular weight constituents. METHODS: Using an avidin-biotin-peroxidase technique, lysosomal proteases and alpha 1-proteinase inhibitor were examined in the trabecular meshwork of 23 human eyes with donor ages ranging from 2 to 90 years. These eyes were categorized into three age groups (< or = 20, 21 to 49, and > or = 50 years). Histochemical staining for lysosomal hydrolases was also performed on frozen sections of 20 human eyes. The staining was analyzed by an image analyzer and the levels of lysosomal proteases were further measured by biochemical assays. RESULTS: The trabecular meshwork from all the eyes stained intensely against antibodies to cathepsins B and G and alpha 1-proteinase inhibitor. The staining for elastase was weaker but evident. Image analyses revealed that the staining intensity for each protease or inhibitor was similar in all age groups. The staining in the uveal meshwork appeared to be the strongest among all the trabecular meshwork regions. Biochemical assays of tissue extracts confirmed that the enzyme and inhibitor levels were comparable among the three donor age groups. Activities of two lysosomal hydrolases, acid phosphatase and acid esterase, were also found in trabecular meshwork cells of 20 eyes. No apparent difference in enzyme activities was found with increasing age, and variation related to region was not observed. CONCLUSIONS: This study demonstrated the age-independent distribution of a variety of lysosomal enzymes and a protease inhibitor in the human trabecular meshwork. The presence of these proteins suggests a possible role in the metabolic operation of the trabecular meshwork.     

Accommodation of a D-Phe residue into a right-handed 3(10)-helix: structure of Boc-D-Phe-(Aib)4-Gly-L-Leu-(Aib)2-OMe, an analogue of the amino terminal segment of antiamoebins and emerimicins

Recently an unstable trinucleotide CTG repeat, located within the 3' untranslated region of a gene on 19q13.3 was discovered in kindreds with myotonic dystrophy (DM). The age-of-onset/severity of DM shows a good correlation with CTG repeat size, and pedigrees and data reported to date have shown a striking trend toward amplification of the size of the CTG repeat during transmission from parent to child. The amplification has been accepted as the biological explanation for anticipation in the clinical severity observed in many families with DM. In this paper we report on 3 families where CTG amplification decreased during transmission from parent to child. In one case there was a gene conversion event, while in the remaining 2 there was a simpler reduction in the size of the repeat length. The changes appear to have been accompanied by a reduction in clinical severity in the child when compared to the parent. These observations are discussed in terms of their clinical implications and the biases that may exist in much of the reported data.     

Simulation of sulfide buildup in wastewater and atmosphere of sewer networks.

A model concept for prediction of sulfide buildup in sewer networks is presented. The model concept is an extension to--and a further development of--the WATS model (Wastewater Aerobic-anaerobic Transformations in Sewers), which has been developed by Hvitved-Jacobsen and co-workers at Aalborg University. In addition to the sulfur cycle, the WATS model simulates changes in dissolved oxygen and carbon fractions of different biodegradability. The sulfur cycle was introduced via six processes: 1. sulfide production taking place in the biofilm covering the permanently wetted sewer walls; 2. biological sulfide oxidation in the permanently wetted biofilm; 3. chemical and biological sulfide oxidation in the water phase; 4. sulfide precipitation with metals present in the wastewater; 5. emission of hydrogen sulfide to the sewer atmosphere and 6. adsorption and oxidation of hydrogen sulfide on the moist sewer walls where concrete corrosion may take place.     

Enzymatic biodiesel production: Technical and economical considerations

It is well documented in the literature that enzymatic processing of oils and fats for biodiesel is technically feasible. However, with very few exceptions, enzyme technology is not currently used in commercial‐scale biodiesel production. This is mainly due to non‐optimized process design and a lack of available cost‐effective enzymes. The technology to re‐use enzymes has typically proven insufficient for the processes to be competitive. However, literature data documenting the productivity of enzymatic biodiesel together with the development of new immobilization technology indicates that enzyme catalysts can become cost effective compared to chemical processing. This work reviews the enzymatic processing of oils and fats into biodiesel with focus on process design and economy.     

Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1-161) in experimental venous thrombosis--a comparison with low molecular weight heparin

The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI1-161), which lacked the third Kunitz-type domain and the basic c-terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2: LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI1-161. TFPI1-161 reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also significantly reduced in those doses. The antithrombotic properties of TFPI1-161 (1.0-10.0 mg/kg) measured as thrombus weight, frequency of thrombosis and frequency of occlusive thrombosis was equivalent to the anti-thrombotic properties of LMWH. In the anti-FXa, APTT and PT-assays TFPI1-161 displayed a dose dependent increase of activity. Recombinant-TFPI1-161 did not influence the anti-FIIa-assay. No haemorrhagic side effects were noted.     

Design and Characterization of the CLIMPAQ,Chamber for Laboratory Investigations of Materials,Pollution and Air Quality*

A test chamber has been developed in order to provide a small and simple emission testing facility capable of testing construction products in a climate where the important climatic parameters such as temperature, ventilation rate and air velocity can be varied independently around typical indoor values. The test chamber CLIMPAQ is made of panes of window glass. Other main surface materials are stainless steel and eloxated aluminium. The chamber has a volume of 50.9 litres and is designed to meet the requirements for quantifying air pollution. In this investigation human subjects acted as air pollution judges, and chemical characterization of the air pollution was carried out. Carpet, linoleum, wall paint and seal- ant were tested simultaneously in the CLIMPAQ and in four other chambers ranging from a full-scale chamber of 28 m³ to a field and laboratory emission cell of 3.5· 10^?5m³. Product ranking is the same in all chambers for the sensory measurements. Emission rates based on sensory measurements differ for all products less than 100 % except for tests in a 3-litre chamber where emission rates were higher. Chemical measurements differ up to approximately 10 times for the same product in different chambers. Deviations appear to be the result of different environmental parameters in the various chambers. Low air concentrations or high specific ventilation rates seem to increase emissions, while differences in air velocities and sink properties may also be the cause of differences in emission rates.     

Enalapril versus bendroflumethiazide in type 2 diabetes complicated by hypertension

In a double-blind, double-dummy, randomized, multi-centre study, the effects of bendroflumethiazide vs. enalapril on blood pressure, glycaemic control, lipoprotein concentrations and albuminuria were compared in non-proteinuric, hypertensive type 2 diabetic patients; they were treated for 20 weeks with either bendroflumethiazide 2.5-5.0 mg (n = 59) or enalapril 10-20 mg (n = 55). Age, fasting plasma glucose, HbA1c and BMI were similar in the groups. Systolic and diastolic blood pressure were reduced in both groups. Bendroflumethiazide was accompanied by minor but significant elevations in fasting plasma glucose and serum C-peptide. HbA1c was increased during both treatments. Lipoproteins and urinary albumin/creatinine ratio were stable. Bendroflumethiazide caused a decrease in serum potassium and an increase in serum urate. No significant correlations were observed between the decline in blood pressure and changes in the metabolic risk factors. Baseline levels of age, sex, BMI, blood pressure or urinary albumin/creatinine ratio were not related to changes in blood pressure, metabolic parameters or urinary albumin/creatinine ratio.     

Activated dissociative chemisorption of methane on Ni(100): a direct mechanism under thermal conditions?

The dissociative chemisorption of methane on a Ni(100) single crystal has been studied under thermal conditions as a function of pressure and temperature. The initial sticking coefficient was measured in the pressure range of 0.010–7.0 mbar at temperatures ranging from 375 to 500 K. A strong pressure dependence was observed, consistent with a direct dissociation mechanism under these thermal conditions. This was further confirmed by experiments where the gas at a low pressure was heated by a thermal finger facing the crystal surface. With the thermal finger at the same temperature as the surface, it was possible to ensure that the methane was fully equilibrated to the crystal and an activation energy of 59±1.5 kJ/mol was determined under isothermal conditions.