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Biomedical subjects

N F Johnson

Publications and source records attributed to N F Johnson.

At least 73 records · Page 4Linked to original sources

Effect of asbestos on the P388D1 macrophagelike cell line: preliminary ultrastructural observations.

The ultrastructural effects of mineral dusts on a macrophagelike cell line (P388D1) were studied by transmission electron microscopy. The cells were found to contain virus particles which probably did not exert a cytopathic effect toward the cells. During mitosis the asbestos fibers appeared to be pushed to the periphery of the cell. The distribution of the asbestos in the P388D1 cells was similar to that seen previously in cultured peritoneal macrophages, and it was concluded that the cytotoxic effect of asbestos towards the cells was due to mechanical effects, e.g., by penetrating structures such as the nucleus or phagosomes, by preventing the ordered movement of organelles with the cell or by disrupting the cytoskeletal framework of the cell.

Animals↗

Prednisolone binding to albumin and transcortin in the presence of cortisol.

The protein binding of prednisolone was assessed in a 5% albumin solution and in pooled human serum, alone and in the presence of various amounts of cortisol. Significant displacement of prednisolone from transcortin binding sites occurred with little or no change in transcortin binding capacity or affinity constant for prednisolone, suggesting competitive inhibition of prednisolone binding by cortisol. Little or no displacement of prednisolone from the protein binding sites on albumin occurred though a decrease in the number of binding sites (four vs two), and an increase in the affinity constant for the albumin-prednisolone interaction (4.32 X 10(2) vs 9.43 X 10(2) M-1) occurred in the presence of cortisol. Allosteric conformational changes may occur in albumin structure in the presence of cortisol. These alterations have no effect on the fraction of prednisolone bound to albumin.

Allosteric Regulation↗

Neuron specific enolase (NSE) immunostaining detection of endocrine cell hyperplasia in adult rats exposed to asbestos.

Hyperplasia of endocrine cells in the lung of the adult rat exposed to asbestos has only been characterised so far by electron microscopy as there is a lack of reliable staining techniques for their demonstration at light microscopical level. Neuron specific enolase (NSE), an isoenzyme of the glycolytic enzyme enolase has recently been shown to be present in lung endocrine cells. In this study we reveal a marked endocrine cell hyperplasia at light microscopical level in the lungs of adult rats exposed to asbestos using antibodies to NSE. Very large groups of NSE-immunoreactive cells (20-80) were only observed in the lungs of rats exposed to asbestos for 12 months. In addition smaller groups of cells (2-10) known to be present normally and to decrease with age, were rarely noted in the controls but were frequently detected in the treated rats. Immunoreactive NSE is therefore a very good marker for endocrine cell hyperplasia and thus of early neoplastic changes.

Animals↗

The combined effects of light and acute ischemia on the structure of the rabbit retina: a light and electron microscopic study.

The ultrastructure of the rabbit retina has been investigated to determine the combined effects of light and ischemia. Both eyes of 16 adult Dutch rabbits were exposed to light of an intensity known to be near or below the threshold for ultrastructural changes in the retina. In addition, one eye of each animal was subjected to one of four periods of pressure-induced total acute ischemia. Exposure to light alone resulted in only minor disturbances of the receptor cell outer segments. The remainder of the retina was of normal morphologic appearance. Exposure to the combined insults of light exposure and ischemia produced considerably more damage to the inner and outer retina. Light exposure combined with short periods of ischemia (15 to 30 min) resulted in edema of the pigment epithelium and disturbances of the receptor cell inner and outer segments. Light exposure combined with longer ischemic periods (45 to 60 min) resulted in severe disturbances in the structure of the pigment epithelium, breakdown of the receptor cell outer segments, rupture of the inner segment mitochondria, and severe edema of the neural retina. The implication of this addictive or synergistic action of light and ischemia is discussed.

Animals↗

The post-mortem vacuoles of Schlemm's canal.

A two-part study was conducted in which post-mortem changes were investigated in the baboon outflow system. It was found that the meshwork cells closest to the chamber angle were particularly susceptible to post-mortem advance. Post-mortem vacuoles developed in the endothelium of Schlemm's canal and by light microscopy these structures could be mistaken for giant vacuoles. On the other hand it was shown by electron microscopy that the giant vacuoles which have been implicated in the transendothelial transfer of aqueous humour and post-mortem vacuoles were distinct and separate entities.

Animals↗

Sectioning and imaging hard mineral fibres in biological tissues.

A technique is described which overcomes the problems associated with sectioning biological tissue containing hard mineral fibres. 0.2--0.5 micrometer thick sections were cut with a diamond knife, placed in a folding grid, conventionally stained with uranyl acetate and lead citrate and viewed at an accelerating voltage of 200 kV in the scanning transmission mode.

Animals↗

The permeability of the posterior blood ocular barrier after xenon photocoagulation: a study using fluorescein labelled dextrans.

Xenon photocoagulation burns in the rabbit fundus were studied angiographically with fluorescein labelled dextrans of molecular weights in the range 3000 to 150 000. Recent photocoagulation burns showed dye leakage to all molecular weights used. Angiograms 2 days after burns had been produced showed leakage of dextrans of molecular weights up to and including 70 000 but no leakage of dextran of 150 000 molecular weight. At 7 days after photocoagulation healed burns remained permeable to dextrans of molecular weight 3000 or 20 000, but in the majority of eyes such burns did not leak dextrans of over 40 000 molecular weight. The clinical significance of the selective nature of photocoagulative damage to the posterior blood ocular barrier is discussed.

Animals↗

Preliminary observations of the effect of inhalation of PVC in man and experimental animals.

Attention has been focussed, both in man and experimental animals, on the effects of inhalation of the gas monomer, vinyl chloride. Recently, note is being taken of the possible effects of the inhalation of the polymer in man. The particles in question are those produced commercially as paste polymer or dispersion polymer or having an average diameter of 0.15 micrometers, and accounting for more than 10% of the production in Britain. There are now strict regulations for the control of the monomer gas, but the particles are regarded as nuisance dust and their emission is not covered by specific legislation. Our studies on rats, where both inhalation and implantation methods of exposure have been used, and examination of tissue from human cases exposed to paste polymers, indicate that these small particles can only be regarded as evidence of exposure, and on present evidence there is no indication of causation of significant pulmonary disease. Techniques have been developed by which these particles can be demonstrated in ordinary histological preparations and by transmission electron microscopy.

Aerosols↗

An ultrastructural study of the effects of asbestos fibres on cultured peritoneal macrophages.

The effects of crocidolite and chrysotile fibres on lavaged peritoneal macrophages have been studied by both scanning (SEM) and transmission (TEM) electron microscopy. SEM provided little information (as the surface topography did not reflect the underlying cytoplasmic organization) except that it showed that individual macrophages often partially engulfed many long fibres in a random fashion. TEM revealed the fibres in and protruding from membrane-bound vacuoles, free in the cytoplasm and penetrating the nucleus. The cellular distribution of the fibres is discussed in terms of the cytotoxic nature of the fibres and their ability to produce a selective release of enzymes from the macrophages.

Animals↗

Serum protein binding of prednisolone in four species.

The protein binding of prednisolone in serum from humans, rabbits, dogs, and rats was determined by equilibrium dialysis. Two nonlinear least-squares regression programs were used to characterize transcortin and albumin binding of the steroid. The animal species differed markedly in their ability to bind prednisolone, but the rabbit was most similar to humans in transcortin concentration and affinity constant.

Animals↗

Release of lamellar bodies from alveolar type 2 cells.

The release of lamellar bodies from rat alveolar type 2 cells has been studied during a 12hr dark/12hr light cycle. A proportion of the type 2 cell population was ultrastructurally abnormal. The cellular changes formed a spectrum raninging from mild to severe, culminating in rupture of the cell and release of its contents into the alveolar air space. The majority of aberrant cells were observed in animals killed during the dark period. A holocrine secretory mechanism is suggested for the release of lamellar bodies containing the surface active phospholipids of the alveolar lining. The release of lamellar material by a process of exocytosis was also observed, but only rarely, in spite of the numerous lamellar bodies seen in each cell cross-section.

Animals↗

A study by electron microscopy of the effects of chrysotile and man-made mineral fibres on rat lungs.

The effects of inhalation of rock wool, coated and uncoated glass wool, glass fibre and UICC chrysotile B on the ultrastructure of the rat lung have been investigated. All fibres produced focal fibrosis, type II cell proliferation, an accumulation of cellular debris and lipid material and hyperplasia of both alveolar cells and cells lining the terminal airways. The fibrosis was more marked following inhalation of chrysotile than after exposure to man-made mineral fibre.

Animals↗

The use of electron microscopy in the diagnosis of diffuse mesotheliomas using human pleural effusions.

Transmission electron microscopy has been found to be of greater value than scanning electron microscopy in the differential diagnosis of mesothelial reaction, malignant mesothelioma and metastatic carcinoma. It is possible to remove identified cells from slides for transmission electron microscopy, and this is particularly valuable when an urgent diagnosis is required.

Adenocarcinoma↗

High-performance liquid chromatographic assay of sulfapyridine and acetylsulfapyridine in biological fluids.

A high-pressure liquid chromatographic method for the sensitive, rapid, and specific determination of sulfapyridine and its N-acetyl derivative in plasma and saliva was developed. A cyano-bonded, reversed-phase, high efficiency column was used. The system detected these sulfonamides in serum to 0.25 mg/liter and within only 6 min. Sulfapyridine was separated from its acetyl derivative with little interference from other drugs. The assay reproducibility was within 3%. The assay was highly useful for routine monitoring of patients receiving sulfasalazine for inflammatory bowel disease.

Acetylation↗

Vitreo-scleral fluid transfer in the rabbit.

Experiments were carried out to see whether a radioactive tracer placed in the vitreous of a rabbit eye could be detected on the sclera. A solution of Xenon-133 dissolved in saline was injected into the vitreous of six rabbits and collecting tubes containing activated charcoal were placed on the sclera. The presence of Xenon in these tubes confirmed that vitreoscleral transfer had occurred. It was calculated that on average, 2% of the Xenon had appeared over the whole sclera. A mathematical analysis of the shape of the activity curve of the tracer on the sclera revealed that its appearance was probably due to diffusion across the outer layers of the eye.

Animals↗