Smoking impairs alveolar macrophage activation after inert dust exposure

Magnetopneumography was applied to investigate intracellular phagosome motion in alveolar macrophage cells of healthy subjects (non-smokers and smokers). Ingested magnetic microparticles are inhaled and phagocytized by alveolar macrophages within hours. Thereby the particles are transferred into phagolysosomes. After magnetization the particles produce a macroscopic magnetic field of the lungs. Cellular motility causes a decay of the field (relaxation) by stochastic disorientation of the dipole particles (phagolysosomes) in the cells. Our studies have shown that the deposition of magnetite test particles induces a non-specific activation of the macrophage cells with a faster relaxation. This activation vanishes within the first day after particle deposition. This macrophage activation due to dust exposure was not present in smokers. It follows that cigarette smoking either causes a damage of the cellular defense or causes an adaptation of the macrophage cells to the permanent cigarette smoke inhalation.     

Large porous particles for pulmonary drug delivery

A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with mass densities less than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs' natural clearance mechanisms until the inhaled particles delivered their therapeutic payload. Inhalation of large porous insulin particles resulted in elevated systemic levels of insulin and suppressed systemic glucose levels for 96 hours, whereas small nonporous insulin particles had this effect for only 4 hours. High systemic bioavailability of testosterone was also achieved by inhalation delivery of porous particles with a mean diameter (20 micrometers) approximately 10 times that of conventional inhaled therapeutic particles.     

Effect of microgravity and hypergravity on deposition of 0.5- to 3-micron-diameter aerosol in the human lung

We measured intrapulmonary deposition of 0. 5-, 1-, 2-, and 3-micron-diameter particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and at approximately 1.6 G. Subjects breathed aerosols at a constant flow rate (0.4 l/s) and tidal volume (0.75 liter). At 1 G and approximately 1.6 G, deposition increased with increasing particle size. In microG, differences in deposition as a function of particle size were almost abolished. Deposition was a nearly linear function of the G level for 2- and 3-micron-diameter particles, whereas for 0.5- and 1.0-micron-diameter particles, deposition increased less between microG and 1 G than between 1 G and approximately 1.6 G. Comparison with numerical predictions showed good agreement for 1-, 2-, and 3-micron-diameter particles at 1 and approximately 1.6 G, whereas the model consistently underestimated deposition in microG. The higher deposition observed in microG compared with model predictions might be explained by a larger deposition by diffusion because of a higher alveolar concentration of aerosol in microG and to the nonreversibility of the flow, causing additional mixing of the aerosols.     

Variation in cytokines induced by particles from different prosthetic materials

Particles of prosthetic material stimulate macrophages to release cytokines, which may cause bone loss and loosening of the prosthesis. This study investigates the possibility that particles of different prosthetic materials may induce different cytokines and thus have different effects on bone remodeling. The in vitro response of human monocytes to particles of cast and forged cobalt chrome alloy, stainless steel, and titanium aluminum vanadium alloy were compared. There was no difference in the biologic response to cobalt-chrome particles derived from cast or forged material. Cobalt-chrome particles were toxic to the cells, but titanium aluminum vanadium particles did not affect cell viability. Stainless steel particles were approximately 10 times more toxic than were cobalt-chrome particles. All particles induced the release of tumor necrosis factor and interleukin 1 beta; stainless steel particles were the most potent stimulators of interleukin 1 beta; titanium aluminum vanadium particles were the strongest stimulators of interleukin 6 and prostaglandin 2. The study showed that particles derived from prosthetic materials of different metal compositions can elicit significantly different biologic responses. Understanding these different responses may help identify materials better suited for prostheses.     

Deposition and dispersion of 1-micrometer aerosol boluses in the human lung: effect of micro- and hypergravity

We performed bolus inhalations of 1-micrometer particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and in approximately 1.6 G. Boluses of approximately 70 ml were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 200 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The deposition, dispersion, and position of the bolus in the expired gas were calculated from these data. For Vp >/=400 ml, both deposition and dispersion increased with Vp and were strongly gravity dependent, with the greatest deposition and dispersion occurring for the largest G level. At Vp = 800 ml, deposition and dispersion increased from 33.9% and 319 ml in microG to 56.9% and 573 ml at approximately 1.6 G, respectively (P < 0.05). At each G level, the bolus was expired at a smaller volume than Vp, and this volume became smaller with increasing Vp. Although dispersion was lower in microG than in 1 G and approximately 1.6 G, it still increased steadily with increasing Vp, showing that nongravitational ventilatory inhomogeneity is partly responsible for dispersion in the human lung.     

Non-dendritic Structural Changes in Al–7Si Alloy Cast Through Rapid Slurry Formation (RSF) Process

Rapid slurry formation (RSF) is a semi-solid metal forming technique, which is based on a so-called solid enthalpy exchange material. The beauty of the process is that the slurry is controlled by relative added amounts of the alloy system used. It is not necessary to accurately control the heat flux to surrounding media such as, crucible or mould. In the present investigation 15?% solid fraction in Al?C7Si alloy slurry has been produced by RSF method. The slurry so prepared was cast in gravity die cast mould with water cooling arrangement. Thus ingot of size 30?cm?×?5?cm?×?2.5?cm could be produced. The microstructure showed rosette and globular type ??-Al morphology. Tensile properties evaluated were higher than as cast Al?C7Si alloy. During slurry formation coarsening of particles was experimentally investigated and also theoretically described by Lifshitz-Slyozov-Wagner (LSW) theory and convective mass flow equations.     

Detection of circulating antigen-antibody complexes by their inhibitory effect on the agglutination of IgG-coated particles by rheumatioid factor of Clq

The agglutination of Ig-coated particles by human RF or Clq can be inhibited by Ig aggregates or AgAb complexes. The effect of Ig class was studied by means of agarose-linked human monoclonal Igs. RF was inhibited by all subclasses of IgG and IgA but not by IgM, whereas Clq reacted with IgM, IgG3 and IgG1. Heat-aggregated IgG3 was fractionated by gel-filtration on Ultrogel. Inhibition was restricted to certain fractions of aggregates, viz (IgG3) approximately 7 and (IgG3) approximately 21 for RF, and (IgG3) approximately 10, (IgG3) approximately 14 and (IgG3) approximately 27 for Clq. In a precipitin curve experiment, it was found that RF was inhibited by soluble complexes over an extended range of AgAb ratios, the inactivation of Clq being limited to complexes with 2-5 times antigen excess. Inhibiting factors were found in patients with various diseases and, at low titres, in 22% of healthy people. In 27% of patients' sera, the inhibitors were demonstrable by Clq only after removal of endogenous RF by adsorption on insolubilized IgG. In several patients endogenous agglutinating activity and direct inhibitory activity tended to alternate during the course of the disease. Sera from various patients were also filtrated on Ultrogel and the elution was monitored by immunoassay of IgA, IgM and IgG, as well as by the two inhibition tests. The inhibiting factors were distributed over several peaks which only partially coincided with the elution profiles of IgG and IgM.     

On the nature of rat hepatic and mouse olfactory sulfotransferases

Seasonal differences in the particle size fractions and mass loadings of household dust deposited on indoor surfaces were examined in four New Jersey homes. Housedust was collected during a 30-day period on non-electrostatic polyethylene sample plates on which a glass slide had been placed. In each home two samples were collected at a height of 1.5 m and two were collected at a height of 0.3 m above the floor. Dust samples were obtained from each home during a summer and winter collection period. Particle size measurement was completed using an adaptation of a Meridian ACAS 570 Interactive Laser Cytometer. Results indicated that the dust mass deposited on household surfaces during the summer was greater than during the winter. The arithmetic mean mass deposition rate for all houses was 0.37 +/- 0.13 microgram/cm2/day during the summer and 0.22 +/- 0.13 microgram/cm2/day during the winter. The total number of particles deposited, however, was greater during the winter than during the summer. The increase in winter time particle number was caused by greater numbers of particles with an equivalent spherical diameter < 2.5 microns. The most probable source of these particles was winter time combustion emissions within the residences and the subsequent particle deposition on household surfaces. The greater mass loadings measured on the low sampling plates during the summer were associated with a greater number of particles with an equivalent spherical diameter > 5 microns. In the winter, however, the particle mass and number loadings were similar at both heights. These results suggested that ventilation of the house during the summer allowed resuspended particles to enter which led to the higher levels of settled dust. Measurement of contaminant levels in housedust for exposure estimation therefore, should account for the seasonal and height differences in dust mass, and collect representative fractions of housedust that are available for human contact. Furthermore, since over 99% of the particles on indoor surfaces were < 50 microns any indirect sampling technique for dermal exposure estimation should have collection efficiencies similar to the hand of particles < 50 microns.     

Erythrocytes from healthy smokers bind more bilirubin than the erythrocytes from healthy non-smokers

Cigarette smoking is an adverse prognostic factor for health. Its damaging effects on many enzymatic and cellular activities are well known. The present study was carried out to evaluate whether there is a difference in the binding of bilirubin to the erythrocytes from healthy smokers and non-smokers. The results suggest that the binding of bilirubin to the erythrocytes from healthy smokers as well as in vitro smoked erythrocytes is significantly higher than that of healthy non-smokers.     

Regional deposition of inhaled particles in human lungs: comparison between men and women

We measured detailed regional deposition patterns of inhaled particles in healthy adult male (n = 11; 25 +/- 4 yr of age) and female (n = 11; 25 +/- 3 yr of age) subjects by means of a serial bolus aerosol delivery technique for monodisperse fine [particle diameter (Dp) = 1 micron] and coarse aerosols (Dp = 3 and 5 micron). The bolus aerosol (40 ml half-width) was delivered to a specific volumetric depth (Vp) of the lung ranging from 100 to 500 ml with a 50-ml increment, and local deposition fraction (LDF) was assessed for each of the 10 local volumetric regions. In all subjects, the deposition distribution pattern was very uneven with respect to Vp, showing characteristic unimodal curves with respect to particle size and flow rate. However, the unevenness was more pronounced in women. LDF tended to be greater in all regions of the lung in women than in men for Dp = 1 micron. For Dp = 3 and 5 micron, LDF showed a marked enhancement in the shallow region of Vp 200 ml. Total lung deposition was comparable between men and women for fine particles but was consistently greater in women than men for coarse particles regardless of flow rates used: the difference ranged from 9 to 31% and was greater with higher flow rates (P < 0.05). The results indicate that 1) particle deposition characteristics differ between healthy men and women under controlled breathing conditions and 2) deposition in women is greater than that in men.     

Effect of strain rate on damage evolution in a cast Al-Si-Mg base alloy

An important aspect of damage evolution in cast Al-Si-Mg base alloys is fracture/cracking of Si particles. This microstructural damage is quantitatively characterized as a function of strain rate in the range 10⁻⁴ to 3.7 × 10⁺³, at an approximately constant uniaxial compressive strain level (20 to 25 pct). It is shown that the fraction of damaged silicon particles, their average size, and size distribution do not vary significantly with the strain rate, and at all strain rates studied, larger Si particles are more likely to crack than the smaller ones. However, the stress-strain curves are sensitive to the strain rate. These observations have implications for modeling of deformation and fracture of cast components under high strain rate crash conditions.     

Development of a membrane oxygenator for ECMO using a novel fine silicone hollow fiber

One of the limitations of conventional silicone hollow fiber oxygenators compared with microporous membrane oxygenators is poor gas permeability. However, the silicone hollow fiber is free from plasma leakage, which is the major life limiting factor of the microporous membrane oxygenator. It has been difficult to fabricate a fine, thin hollow fiber for reduction of resistance to gas permeability because of the poor mechanical strength of conventional silicone materials. The authors developed a novel silicone material with sufficient mechanical strength, and a fine silicone hollow fiber with a diameter of 30 microns and wall thickness of 50 microns, which is approximately half that of a conventional silicone hollow fiber. Using this newly developed silicone hollow fiber, the authors developed a compact extracapillary flow membrane oxygenator. The oxygenator consists of fine silicone hollow fibers inserted in a housing made of polycarbonate. The housing is a cylindrical case, 20 cm long and 55 mm in inside diameter. The hollow fibers are cross-wound. The surface area of the membrane is 2.0 m2, and priming volume is 230 ml. Gas transfer performance of the newly developed oxygenator was evaluated by in vitro experiments. Oxygen and carbon dioxide transfer rates were 195 ml/min and 165 ml/min, at a blood flow rate 3 L/min. The novel silicone membrane oxygenator developed in this study can be used for extended duration in such applications as extracorporeal membrane oxygenation.     

Microstructural refinement of an As-cast Al-12.6 wt pct Si alloy by repeated thermomechanical treatment to produce a heavily deformable material

A certain degree of cold working is advantageous in developing a fine microstructure with minute silicon crystals for eutectic and/or hypereutectic Al-Si cast alloys. A novel process, repeated thermomechanical treatment (RTMT), was applied to an Al-12.6 wt pct Si cast alloy. The process involves multiple-pass cold working (less than a 20 pct reduction in section area) and heat treatment at 793 K for 3.6 ks. Cold-work annealing was repeated up to about an 80 pct reduction in section from the beginning. The RTMT material showed a refined microstructure with high ductility. Most silicon crystals were fragmented to only a few micrometers and were spheroidized. The RTMT material showed such marked plasticity that it could be wrought up to a 99 pct reduction in section at room temperature. The Cold-worked RTMT materials exhibited an excellent balance between tensile strength and elongation and a higher strain hardening than the cast material.     

Encapsulation of OKT3 cells in hollow fibers

Encapsulation of an OKT3 cell line in hollow fibers was evaluated in vitro and in vivo. The cell line is a mouse hybridoma producing immunoglobulin G2a (IgG2a) against CD3 human T lymphocytes and thus may function as a nonspecific activation system of a subpopulation of human T lymphocytes. For encapsulation purpose, hollow fibers of polypropylene K600 PP Accurel (Akzo, Germany) were selected. Hollow fibers were siliconized to improve membrane biocompatibility for in vivo experiments. The siliconized hollow fibers exhibited acceptable diffusive permeability (P) [ml/min/m2] for small solutes (for creatinine, p = 63.9 +/- 2.0, n = 3) and larger solutes (for albumin, p = 16.9 +/- 1.9, n = 3; for IgG, p = 1.0 +/- 0.2, n = 3). The 12 cm long hollow fibers were filled with a suspension of OKT3 cells of an average density of 10(6) cells/ ml, and both ends were sealed. The encapsulated cells were cultivated in RPMI 1640/10% CS medium at 37 degrees C, 5% CO2 for a period of 3 to 4 days. After the culture period, the medium was tested on human peripheral blood lymphocytes for the presence of anti-CD3 antibody and read in a flow FACS-trac cytometer (Becton Dickinson Immunocytochemistry Systems, San Diego, CA). The tightness of hollow fiber sealing was tested with a bubble point method. The number of cells increased after cultivation by four- to nine-fold on average (n = 11). Ten experiments were performed in vivo with OKT3 cells encapsulated in hollow fibers and implanted subcutaneously into mice for 3 days. In 50% of the experiments, some anti-CD3 antigens on human lymphocytes were found; however, the difference, in comparison with control, in percent of CD3+ was insignificant. In conclusion, the hollow fiber method for cultivation of hybridoma cells in vitro allows for separation of cells from the medium containing secreted anti-CD3 antibodies and is effective in maintaining cell viability. In vivo application needs additional study.     

Identification of oxidized low density lipoprotein in human renal biopsies

BACKGROUND: Intraglomerular lipid deposition is frequently observed in routine renal biopsies, and it has been suggested that lipid peroxidation of low density lipoprotein (LDL) may be implicated in the pathogenesis of progressive glomerulosclerosis. We have examined whether oxidized LDL (Ox-LDL) is present in the glomeruli of patients with renal disease and whether intrinsic human glomerular cells express NADPH-oxidase (a superoxide-generating enzyme found in professional phagocytes). METHODS: Immunocytochemical study was performed on 939 renal biopsy specimens, using monoclonal antibodies (mAbs) OL-10, 48 and 449, and polyclonal antibody against human apolipoprotein (apo) B. Mouse mAb OL-10 recognizes malondialdehyde (MDA)-modified peptide epitope, and mAbs 48 and 449 react with alpha and beta subunits of cytochrome b558, an essential component of NADPH-oxidase. RESULTS: Sixty-two (6.6%) of the 939 patients with renal disease exhibited a staining for MDA-altered protein or Ox-LDL in the glomeruli, mainly in the sclerotic segments or mesangial areas. Group 1 patients with heavy Ox-LDL deposition mainly in the sclerotic segments showed a higher frequency of renal insufficiency and heavy proteinuria and a greater degree of glomerulosclerosis, compared to those in group 2 with mesangial Ox-LDL staining. The distribution of MDA protein epitopes, in general, paralleled the deposition of apo B epitopes. Immunoelectron microscopy of ultrathin frozen sections showed the presence of immunogold particles for mAbs 48 and 449 in the cytoplasm of resident glomerular cells of both normal and diseased kidneys. When immunoblotted with mAb OL-10, one band from the IgA nephropathy and focal segmental glomerulosclerosis groups at approximately 260 kD was labeled, whereas immunostaining of normal control samples revealed no staining. CONCLUSIONS: These results indicate that Ox-LDL is present mainly in the lesions of glomerulosclerosis and mesangial areas in human renal biopsies. They also suggest that patients with heavy Ox-LDL accumulation in the sclerotic segments of glomeruli have more advanced renal disease than those with mesangial Ox-LDL and that resident glomerular cells generate cytochrome b558, the potential of which may not suffice to induce peroxidation of LDL in the diseased glomeruli.     

Smoking-related increase of O6-methylguanine-DNA methyltransferase expression in human lung carcinomas

Eighty-three non-small cell lung carcinomas (NSCLC) of previously untreated patients were analysed for expression of O6-methylguanine-DNA methyltransferase (MGMT) by means of immunohistochemistry. Expression of MGMT was detected in 62 of 83 tumours (75%). There was a significant difference in MGMT staining between smokers and non-smokers (P = 0.001). Tumours of smokers expressed more frequently MGMT than tumours of non-smokers. There was a trend of MGMT expression to be higher in tumours of patients smoking >20 cigarettes/day than patients smoking <20 cigarettes/day. Abstinence from smoking resulted in a significant decrease in MGMT expression (lin reg r = -0.59, P < 0.05). These results demonstrate that MGMT expression in human lung carcinomas is influenced by smoking habits of the patients.     

Interim report on the radiosurgical treatment of cerebral arteriovenous malformations. The influence of size, dose, time, and technical factors on obliteration rate

During the authors' initial 4-year experience with radiosurgery using the Leksell cobalt-60 gamma unit, they treated 121 patients with cerebral arteriovenous malformations (AVMs). The radiosurgical dose to the margin of the nidus was 20 Gy for lesions less than 2.0 cm in diameter (volume < or = 4.2 cm3); 18 Gy for malformations 2.1 to 3.0 cm in diameter (volume 4.2-14.1 cm3); and 16 Gy for malformations greater than 3.0 cm (volume > 14.1 cm3). Fifty-one patients underwent follow-up angiography between 1 and 3 years after treatment, and complete obliteration of the nidus was confirmed in 38 (74.5%) of these patients. Thirty-two (74.4%) of 43 AVMs with volumes of 10 cm3 or less and six (75%) of eight larger AVMs (volume 11-30 cm3) showed complete obliteration. Analysis of the time course of AVM nidus shrinkage and obliteration showed that most of the radiosurgically induced effect had occurred by 36 months after treatment. Retrospective analysis of the dose plans for 10 AVMs that were not obliterated by 36 months after gamma knife radiosurgery at the authors' institution (eight cases) or elsewhere (two cases) revealed that six AVMs had not been covered completely by the prescribed isodose. Six (5%) of the 121 patients developed neurological deficits as a direct result of radiosurgical treatment. The authors infer from these data that malformations up to 30 cm3 in volume (approximately 4.0 cm in average diameter) can be treated effectively with an acceptably low complication rate using a radiosurgical dose of 16 Gy to the margin of the nidus. The obliteration rate for the larger malformations that were treated with a dose of 16 to 18 Gy appears to be similar to that for smaller ones treated with 18 to 20 Gy. As more experience accrues using radiosurgery to treat AVMs, patient selection criteria and the variables associated with successful obliteration of the nidus should become more clearly defined.     

Influence of temperature on irritation in the hand/forearm immersion test

The time-dependent appearance of signs of cell death was investigated in human skin wounds using in situ end labeling of DNA fragments (ISEL). In the dermal layer an average of not more than 0.3 positively stained fibroblastic cells/0.01 cm x 0.01 cm was found up to a postinfliction interval of approximately 6 h. Average numbers exceeding 1 positive cell/0.01 cm x 0.01 cm were first detectable in a skin wound after 24 h. Therefore, average numbers greater than 1 labeled cell/ 0.01 cm x 0.01 cm indicate a postinfliction interval of approximately 1 day. An increase in the average number of positively stained cells occurred with increasing wound age. Values exceeding 3 cells/0.01 cm x 0.01 cm were first detectable 19 days after wound infliction. Accordingly, values of more than 3 labeled cells indicate a postinfliction interval of approximately 3 weeks or more. Since low numbers of labeled fibroblastic cells or even negative results were found in wounds of advanced age, only positive results provide information which can be useful for a forensic age estimation of human skin wounds.     

Structural characteristics of a sormatt type alloy powder produced by electroerosion disintegration in water

Conclusions The electroerosion disintegration of a manganese-containing Sormait type alloy in water yields powders of spherical particle shape. A coarse (>40-m) fraction of such a powder consists mainly of hollow particles, which are the most suitable for the flame-spray deposition of coatings. The particles of the powder have a homogeneous fine-grained structure differing radically from that of the starting alloy, and surpass the latter in microhardness. The powder is passivated by Fe₃O₄ films which increase its resistance to attack by corrosive environments. EE powders may find application for the deposition of protective coatings.A group of Fe-base C-Mn-Si-Cr-Ni hard-facing alloys-Publisher.Translated from Poroshkovaya Metallurgiya, No. 10(274), pp. 66–71, October, 1985.