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Biomedical subjects

P Ingram

Publications and source records attributed to P Ingram.

At least 37 records · Page 2Linked to original sources
PubMed1988

Quantitative microchemical imaging of calcium in Na-K pump inhibited heart cells.

Quantitative electron probe X-ray imaging techniques have been utilized to determine simultaneously the element content within a single cultured embryonic chick heart cell and its intracellular compartments as well as the average elemental content of several heart cells within a population. These features of microchemical imaging have permitted establishment of data regarding: (1) the heterogeneity of calcium accumulation in mitochondrial, cytoplasmic and nuclear compartments under conditions which elevate total cell calcium without producing irreversible cell injury; and (2) the variability of calcium accumulation from cell to cell within the population sampled. The results indicate that during Na-K pump inhibition (K-free HT-BSS, 10(-4) M ouabain, 60 min) elevation of mitochondrial calcium, measured in situ by electron probe X-ray microanalysis, to levels more than 100 times greater than in the basal state, may not cause irreversible mitochondrial uncoupling and cell death.

Calcium↗
PubMed1988

Frontiers in electron probe microanalysis: application to cell physiology.

The application of electron probe microanalysis techniques, using X-ray and electron energy loss instruments, to problems in cell physiology is reviewed. The details of the special methodological requirements for the analysis of cryosections at high spatial resolution in an analytical electron microscope are discussed together with a comprehensive review of data obtained on major organ systems and cell types.

Animals↗
PubMed1988

Microprobe analysis of chlorpromazine pigmentation.

We describe the histochemical, ultrastructural, and microanalytical features of a skin biopsy specimen obtained from a patient with chlorpromazine pigmentation. Golden-brown pigment granules were present in the dermis, predominantly in a perivascular arrangement. The granules stained positively with the Fontana-Masson stain for silver-reducing substances and negatively with Perl's stain for iron. Electron microscopy revealed dense inclusion bodies in dermal histiocytes, pericytes, endothelial cells, and Schwann cells, as well as lying free in the extracellular matrix. These "chlorpromazine bodies" were quite dense even in unosmicated, unstained ultrathin sections, indicating that the pigmentation is related, at least in part, to the inclusions. Microprobe analysis of the chlorpromazine bodies revealed a striking peak for sulfur, which strongly suggests the presence of the drug or its metabolite within these inclusions.

Adult↗
PubMed1986

Heterogeneity of calcium compartmentation: electron probe analysis of renal tubules.

The objective of this study has been to determine the intracellular localization of calcium in cryofixed, cryosectioned suspensions of kidney proximal tubules using quantitative electron probe X-ray microanalysis. Two populations of cells have been identified: 1) "Viable" cells, representing the majority of cells probed, are defined by their relatively normal K/Na concentration ratio of approximately 4:1. Their measured Ca content is 4.1 +/- 1.4 (SEM) mmol/kg dry wt in the cytoplasm and 3.1 +/- 1.1 mmol/kg dry wt in the mitochondria, or an average cell calcium content of approximately 3.8 mmol/kg dry wt. 2) "Nonviable" cells, defined by the presence of dense inclusions in their mitochondria and a K/Na concentration ratio of approximately 1. The Ca content is 15 +/- 2 mmol/kg dry wt in the cytoplasm and 685 +/- 139 mmol/kg dry wt in the mitochondria of such cells. Assuming 25 to 30% of the cell volume is mitochondrial, the overall calcium content of such nonviable cells is approximately 210 mmol/kg dry wt. The presence of these inclusions in 4 to 5% of the cells would account for the average total Ca content measured in perchloric acid extracts of isolated proximal tubule suspensions (approximately equal to 18 nmol/mg protein or 12.6 mmol/kg dry wt). Whole kidney tissues display a large variability in total Ca content (4.5 to 18 nmol/mg protein, or 3.4 to 13.5 mmol/kg dry wt), which could be accounted for by inclusions in 0 to 4% of the cells. The electron probe X-ray microanalysis (EPXMA) data conclusively demonstrate that the in situ mitochondrial Ca content of viable cells from the kidney proximal tubule is low and support the idea that mitochondrial Ca may regulate dehydrogenase activity but probably does not normally control cytosolic free Ca.

Animals↗
PubMed1985

Microprobe analysis in human pathology.

This tutorial paper reviews the literature on the application of microprobe analysis to practical problems in diagnostic human pathology. The goal is to allow the reader ready access to the literature on specific clinical problems. Specimen preparation and commonly encountered artifacts are also considered. It is concluded that energy dispersive x-ray microanalysis and back-scattered electron imaging are at present the most generally useful microprobe techniques for clinical work, and are no longer solely research tools. The findings often have diagnostic, therapeutic, and/or legal implications.

Body Fluids↗
PubMed1984

Effect of di(2-ethylhexyl) phthalate on DNA repair and lipid peroxidation in rat hepatocytes and on metabolic cooperation in Chinese hamster V-79 cells.

Experiments were conducted to test the hypothesis that the hepatocarcinogenicity of di(2-ethylhexyl) phthalate (DEHP) is due to its ability to produce DNA damage, either directly or as a result of the proliferation of peroxisomes and accompanying increased production of H2O2 and other DNA--damaging oxygen radicals induced by sustained exposure to the plasticizer. DNA repair, as assessed by the autoradiographic measurement of unscheduled DNA synthesis (UDS), was not observed in primary rat hepatocytes exposed in vitro to 10(-5)-10(-2) M DEHP or in vivo by a single gavage dose of 5 g DEHP/kg body weight administered 2, 15, or 24 h prior to the isolation of hepatocytes. Thus, DEHP does not appear to directly produce repairable DNA damage in rat hepatocytes. Sustained feeding of DEHP at a dietary concentration of 2% led to a marked proliferation of peroxisomes in the liver after 4 wk. Additional administration of a single gavage dose of 5 g DEHP/kg body weight to animals fed the 2% diet for 4 or 8 wk, as well as to 4-wk-fed animals that were also pretreated with 3-amino-1,2,4-triazole to inhibit endogenous catalase activity, did not induce any detectable DNA repair in hepatocytes isolated 15 h following the single gavage dose of DEHP. Lipid peroxidation measured in the 9000 X g supernatant of livers from animals treated with a single dose of 5 g DEHP/kg body weight or the 2% DEHP diet for 6 wk plus a single dose of 5 g/kg body weight did not differ from controls. These findings suggest that DEHP does not elicit DNA damage or lipid peroxidation in liver consequent to the proliferation of peroxisomes resulting from prolonged administration. In addition, at noncytotoxic concentrations DEHP failed to produce a positive response in the Chinese hamster V-79 metabolic cooperation assay for tumor promoters.

2-Acetylaminofluorene↗
PubMed1984

Ultrastructural comparison of ion beam and radiofrequency plasma etching effects on biological tissue sections.

Three dry etching techniques (Ar+ ion beam, O2+ ion beam, O2 radiofrequency electrodeless discharge) were compared with respect to preferential etching and damage to the ultrastructure of glutaraldehyde-fixed Epon-embedded frog skeletal muscle sections. SEM and TEM studies were performed on both unstained and stained (osmium tetroxide, uranyl acetate) sections. Etching effects were observed to differ for the various ion beam or plasma etching techniques. Whereas selective retention of electron dense structures (e.g. Z lines, nuclear heterochromatin) was observed for oxygen plasma etching, preferential etching of these components was observed using O2+ ion beam bombardment. Selectively etched Z lines and etch-resistant nucleoli were observed for both reactive (O2+) and inert (Ar+) ion beam sputtering after sufficiently high ion doses. The above suggest that selective etching under keV ion beam irradiation is related more to physical sputtering processes (momentum transfer) than to the chemical reactivity of the incident ion. Heavy metal post-fixation and staining had no qualitative effect on the nature of the selective etching phenomena. The above findings are significant in that they potentially influence both electron and ion microprobe measurements of etched biological specimens.

Animals↗
PubMed1984

New techniques for imaging and analyzing lung tissue.

The recent technological revolution in the field of imaging techniques has provided pathologists and toxicologists with an expanding repertoire of analytical techniques for studying the interaction between the lung and the various exogenous materials to which it is exposed. Analytical problems requiring elemental sensitivity or specificity beyond the range of that offered by conventional scanning electron microscopy and energy dispersive X-ray analysis are particularly appropriate for the application of these newer techniques. Electron energy loss spectrometry, Auger electron spectroscopy, secondary ion mass spectrometry, and laser microprobe mass analysis each offer unique advantages in this regard, but also possess their own limitations and disadvantages. Diffraction techniques provide crystalline structural information available through no other means. Bulk chemical techniques provide useful cross-checks on the data obtained by microanalytical approaches. It is the purpose of this review to summarize the methodology of these techniques, acknowledge situations in which they have been used in addressing problems in pulmonary toxicology, and comment on the relative advantages and disadvantages of each approach. It is necessary for an investigator to weigh each of these factors when deciding which technique is best suited for any given analytical problem; often it is useful to employ a combination of two or more of the techniques discussed. It is anticipated that there will be increasing utilization of these technologies for problems in pulmonary toxicology in the decades to come.

Environmental Pollutants↗
PubMed1984

Scanning electron microscopic study of the airways in normal children and in patients with cystic fibrosis and other lung diseases.

Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to examine pulmonary tissue from 9 patients with cystic fibrosis (CF), 12 patients with diseases other than CF, and from two surgically resected specimens with no known airways disease. A region of the human airways, the transition zone, was observed between the end of the terminal bronchiole and the type II alveolar cell lining of the respiratory bronchioles. This region was lined predominantly by nonciliated bronchiolar (NCB) cells. Patients with CF exhibited indistinct transition zones, epidermoid metaplasia, large dilated bronchial glands, copious surface mucus, alveolar destruction, and unusual microvilli; no single lesion specific for cystic fibrosis was identified.

Adolescent↗
PubMed1983

Scanning electron microscopy and X-ray microanalysis of foreign bodies associated with Silastic implants in humans.

Polydimethylsiloxane (Silastic) capsules containing megestrol acetate have been implanted in subcutaneous tissue as a method of long-term contraception. Histological studies revealed a granulomatous foreign body reaction around these capsules with birefringent crystals in multinucleated giant cells. Although several authors had interpreted these crystals as steroids, this seemed unlikely since the tissue had been processed with organic solvents. Analysis of these crystals by polarization microscopy, scanning electron microscopy, and X-ray microanalysis demonstrated that the material was talc. The talc was probably introduced as a contaminant from gloves during the implantation. Further analysis showed that capsule fragmentation could not have produced the material since Silastic particles could not be detected.

Contraceptive Agents↗
PubMed1983

Experience with ceftazidime in cystic fibrosis.

Twelve adults and children with cystic fibrosis received a total of 17 courses of ceftazidime for the treatment of an acute exacerbation of respiratory tract infection. In 6 cases ceftazidime was given as the sole antibiotic. All patients who were clinically assessable were considered to be cured of the acute infection, or improved. Bacteriologically all initial sputum specimens contained Pseudomonas aeruginosa. In 13 instances the organism disappeared during treatment, while in the other 4 the organism remained although the patients improved clinically. Additional organisms, usually Staphylococcus aureus or Haemophilus influenzae, were present in 7 instances. One patient suffered from nausea, palpitations and local skin inflammation on injection whilst being treated with ceftazidime, but the relationship between these adverse effects and ceftazidime was uncertain. The patient tolerated these effects without discontinuation of the drug.

Adolescent↗