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Biomedical subjects

A Reith

Publications and source records attributed to A Reith.

At least 19 recordsLinked to original sources
PubMed1992

Invasion of brain tissue by primary glioma: evidence for the involvement of urokinase-type plasminogen activator as an activator of type IV collagenase.

The immunocharacterization of a metalloproteinase isolated from rat glioma cell conditioned medium is described and confirms that the enzyme is identical to type IV collagenase. Free, active plasminogen activator (PA) and PA-PAI complexes were identified as being secreted by the same cells. Using affinity-purified metalloproteinase we demonstrate that the enzyme can be partially activated by u-PA but not by plasmin in vitro. On the basis of these findings and previous published work we propose a scheme for the proteolytic degradation of normal brain tissue during tumour invasion.

Animals↗
PubMed1992

Comparison between flow cytometry and image cytometry in ploidy distribution assessments in gynecologic cancer.

The DNA content in 37 tumors from 34 women with gynecological cancer was measured by flow cytometry (FCM) and interactive image cytometry (ICM). Agreement was obtained in 81% of cases as regards ploidy levels, but seven tumors (19%) showed different ploidies. Of these, five were classified as diploid by FCM but either aneuploid (three cases) or polyploid (two cases) by ICM. Two other tumors were aneuploid by ICM but polyploid (one case) and unclassifiable (one case) by FCM. All tumors classified as aneuploid by FCM were also aneuploid by ICM, and all tumors classified diploid by ICM were also diploid by FCM. Of six patients whose tumors were classified as euploid (five diploid and one polyploid) by FCM but classified as aneuploid by ICM, five relapsed, and three of these have died of disease. On the basis of these findings, it is concluded that ICM must be performed in cases classified as diploid by FCM to ensure that small subpopulations of aneuploid tumor cells are not overlooked.

Aneuploidy↗
PubMed1992

Quantitative histopathological evaluation of vocal cord dysplasia with particular emphasis on nuclear orientation.

We have applied morphometry on formaldehyde-fixed, H & E-stained diagnostic laryngeal biopsies from 7 patients with mild dysplasia and 7 with severe dysplasia/carcinoma in situ, in search of objective parameters required for reproducible histopathological grading of epithelial dysplasias. Special emphasis has been put upon the individual nuclear polarity as a spatial variable. Also included were 4 specimens with normal epithelium. By means of a semiautomatic digitizing tablet, the nuclear and epithelial area, formfactor and the polarity variation between the longitudinal axes of adjacent nuclei were measured in the basal, parabasal, middle and luminal layers of the epithelium. N:C-ratio, mean values of nuclear area, formfactor or their coefficient of variation could not distinguish between mild and severe dysplasia. The variations in neighboring nuclear polarity, however, revealed a highly significant distinction between mild and severe dysplasia (p less than 0.001). This parameter may therefore have diagnostic potential.

Biopsy↗
PubMed1992

Chemical composition and morphology of welding fume particles and grinding dusts.

Elemental composition and morphology of pure manual metal arc (MMA) welding fumes, pure grinding dust, and combined fume/dust air samples were collected and determined separately under semilaboratory conditions. The base material was stainless steel. The purpose of the present study was to create a "synthetic" work situation under semilaboratory conditions by combining one grinding period and two MMA welding periods and comparing these results with results during welding in a workshop. The duty cycles of pure welding and of pure grinding were also observed. A comparison was also made between metal inert gas (MIG) and MMA welding on stainless steel as well as a nickel-rich alloy under regular conditions. The amount of collected material was determined by weighing the membrane filters before and after exposure, and the element contents were determined by atomic spectroscopy. Other transmission electron microscopy (TEM) filters were used for TEM and computer-image analysis, in which the amount of collected material and its morphological characteristics were observed. The arcing time and the consumption of filler material were estimated for different kinds of electrodes. Chemical analysis showed that the contents of manganese and total chromium were lower in grinding dust than in welding fumes. The contents of hexavalent chromium, Cr(VI), in grinding dust were undetectable. Samples collected in welding shops where concomitant grinding was performed contained about 30% less Cr(VI) than those collected under laboratory conditions during welding only. The sizes and shapes of the particles depend on the welding process and distance of collection from the plume of the fume. To compare laboratory experiments with regular welding situations, the experiment must resemble industrial welding.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromium↗
PubMed1992

A study of tobacco carcinogenesis XLVIII. Carcinogenicity of N'-nitrosonornicotine in mink (Mustela vison).

During tobacco processing and smoking, nicotine and nornicotine give rise to N'-nitrosonornicotine (NNN), a highly abundant, strong carcinogen. NNN is known to exert carcinogenic activity in mice, rats and hamsters. Major target organs for NNN carcinogenicity in the rat are the esophagus and the nasal mucosa, and in the Syrian golden hamster trachea and nasal mucosa. In comparison with the rat, the mink (Mustela vison) has a markedly expanded nasal mucosa. Therefore, we explored in this study whether the mink could serve as a non-rodent model for nasal carcinogenesis using NNN as the carcinogen. Twenty random-bred mink, beginning at the age of 3 weeks, received twice weekly s.c. injections of NNN, a total dose of 11.9 mM per animal over a 38 week period. All of the 19 mink at risk developed malignant tumors of both the respiratory and the olfactory region of the nose within 3.5 years. In most animals the malignant tumors, primarily esthesioneuroepithelioma, invaded the brain. Remarkably, NNN induced no other tumors in the mink. None of the control animals developed nasal tumors nor tumors at other sites during the 3.5 years of the assay. The historical data from the farm did not reveal any spontaneous occurrence of nasal tumors in mink at any age. This study supports the concept that NNN is a proven carcinogen for multiple species of mammals and that the mink can serve as a non-rodent, non-inbred animal model for nasal carcinogenesis, especially since NNN induces only tumors in the nasal cavity in this species and not at other sites, as it does in mice, rats and hamsters.

Animals↗
PubMed1992

How often is dysplasia diagnosed by biopsy or smear examination? Application of a maximum likelihood based method to the assessment of detection rates in the nasal mucosa of nickel workers.

In view of the known increased risk of nasal carcinoma and the high prevalence of dysplastic lesions of the nasal mucosa among nickel workers, regular screening for the existence of possibly precancerous dysplastic lesions is offered to workers in a Norwegian nickel refinery. Unfortunately, available sampling techniques do not allow the identification of all subjects in whom dysplastic changes are present. Independent histological and cytological (brush cytology) diagnoses, obtained for each of a group of 90 workers, have been used to estimate, by a maximum likelihood method, the probabilities that existing dysplastic lesions will be detected by each of these two screening methods. In the group studied, cytology performed rather less well than histology in unambiguously detecting dysplasia. However, when cytological specimens showing irregular (possibly dysplastic) epithelial cells were grouped with those showing clear dysplastic changes, detection probabilities were estimated at 0.52 by histology and 0.57 by cytology. Detection probabilities were estimated to be higher among subjects with a previously known history of dysplasia, particularly by histology (P < 0.01), probably due to larger dysplastic areas. In view of both its greater facility and speed of sampling, and its greater acceptability, brush cytology may be preferable to biopsy sampling for the screening of large numbers of workers at risk.

Biopsy↗
PubMed1991

Specific gain of chromosome 19 in preneoplastic mouse liver cells after diethylnitrosamine treatment.

Most attempts to elucidate primary cytogenetic events have been made on the basis of chromosome analysis of cells from the later stages of tumor development. Hence it is difficult to decide which, if any, of the observed chromosomal alterations are causative rather than consequential in neoplastic development. One approach to understand the role of chromosomal changes in neoplasia is to examine the chromosomal constitution of cells at early stages in the process of carcinogenesis. We have developed a method for direct preparation of metaphase plates of cells from preneoplastic liver nodules and we present herein the first report of nonrandom chromosome changes in solid tumor precursor cells. The results of the cytogenetic analysis demonstrated trisomies/polysomies for chromosome 11 and chromosome 19. A specific increase in the number of chromosome 19 was found in 43% of the 37 plates karyotyped and 25% of the plates demonstrated increase in the number of chromosome 11. The finding shows that gross chromosomal changes such as polysomies may play an important role in the early development of tumors. They further indicate the presence of a gene on chromosome 19 with an essential role either in the initiation or promotion of the neoplastic transformation of hepatocytes.

Animals↗
PubMed1991

Contiguous patterns of c-kit and steel expression: analysis of mutations at the W and Sl loci.

Mutations in either the dominant white-spotting (W) or Steel (Sl) loci of the mouse lead to coat color, primordial germ cell and hematopoietic defects. Consistent with the cell autonomous and microenvironmental nature of W and Sl mutations, respectively, it has recently been shown that W encodes the c-kit receptor tyrosine kinase while Sl encodes a ligand for this receptor. Previous in situ hybridization analysis has shown that both c-kit and steel are expressed in the embryo in anatomical sites known to be affected by W and Sl mutations and in various tissues in which no corresponding phenotype has been described. To investigate the possible involvement of the Kit transduction pathway in developmental processes, we compared the patterns of expression of c-kit and steel in wild-type embryos and in embryos homozygous for severe (lethal) and mild (viable) alleles at the W and Sl loci. In addition, we analyzed the patterns of expression of both genes in adult wild-type and mutant gonads and brain. Both c-kit and steel are contiguously expressed in a wide variety of anatomical locations in both the developing embryo and in the adult. In adult gonads, steel is expressed in the follicular cells of the ovary and in Sertoli cells of the testis, the layers that immediately surround the c-kit expressing germ cells. In adult brain, the complementary patterns are particularly striking in the olfactory bulb, cerebral cortex, hippocampus region and cerebellum. steel expression in brain is probably restricted to neurons in certain areas, while c-kit is expressed in neurons and in some glial cells. Severe mutations in the W or Sl loci result in dramatic reduction or absence of c-kit positive cells in lineages known to be affected by these mutations. In contrast, these mutations do not affect the number or histological organization of c-kit positive cells in the embryonic peripheral or central nervous systems, nor is the number or organization of c-kit positive cells detectably altered in Wv/Wv or Sld/Sld adult brain. Taken together, these results suggest that the Kit signaling pathway is not obligatory for the viability and/or migration of most c-kit expressing cells either because of functional redundancy with another signaling pathway or because the Kit pathway is involved in post-developmental processes of mature cells.

Animals↗
PubMed1990

Role of catalase and oxidative stress in hepatic peroxisome proliferator-induced morphological transformation of Syrian hamster embryo cells.

Several hepatic peroxisome proliferators (HHPs) such as di(2-ethylhexyl)phthalate (DEHP), mono(2-ethylhexyl)-phthalate, clofibrate and tiadenol, induce morphological transformation of Syrian hamster embryo (SHE) cells in vitro. According to one hypothesis, the hepatocarcinogenic effect of HPPs is caused by an oxidative stress due to increased H2O2-production from the strongly induced peroxisomal beta-oxidation of fatty acids. Thus, increased transformation frequencies by HPPs should be obtained when catalase was inhibited by 3-amino-1,2,4-triazole (amitrole). However, co-exposure to HPPs and amitrole did not enhance the transformation frequencies for any of the HPPs. The sensitivity of SHE cells for oxidative agents was studied by using menadione and H2O2. Menadione only induced transformation at a toxic concentration, while H2O2 induced transformation at non-toxic concentrations. To study the generation of oxidative radicals in SHE cells, electron spin resonance was employed. No oxidative radical formation was detected in tiadenol- or DEHP-exposed SHE cells. When menadione or H2O2 were added during the measurements, oxidative radicals were found. A transmission electron microscopic study showed a small number of peroxisomes, and did not reveal any increase in the number of peroxisomes in clofibrate-treated SHE cells.

Amitrole↗
PubMed1990

Nasal mucosa in workers exposed to formaldehyde: a pilot study.

This study evaluates the histological changes, especially the presence of possible precancerous lesions, in the nasal mucosa of workers exposed to formaldehyde. Nasal biopsies of 37 workers occupationally exposed to formaldehyde for more than five years and 37 age matched referents showed a higher degree of metaplastic alterations in the former group. In addition, three cases of epithelial dysplasia were observed among the exposed. These results indicate that formaldehyde may be potentially carcinogenic to man. Combination of this finding with the inconclusive epidemiological studies suggests that formaldehyde is a weak carcinogen and that occupational exposure to formaldehyde alone is insufficient to induce nasal cancer.

Adult↗
PubMed1990

The mouse W/c-kit locus.

The mature cells in the haemopoietic system arise as the result of the extensive developmental and proliferative capacity of pluripotential stem cells. In order to understand the molecular basis for these developmental processes, it will be necessary to identify and characterize the cellular genes that control early steps in haemopoiesis. Mutations at the mouse W locus on chromosome 5 lead to pleiotropic developmental defects, including sterility, coat colour abnormalities, severe macrocytic anaemia and mast cell deficiency. The defects in all these lineages are cell autonomous and intrinsic, suggesting that the W locus encodes a gene product required directly for cellular differentiation. In an attempt to understand this classical mouse developmental mutation, we have demonstrated that the c-kit proto-oncogene, which encodes a transmembrane receptor tyrosine kinase, is very closely linked to W. Several further observations are consistent with the idea that W and c-kit are allelic: first, c-kit is expressed in those cell populations affected by W mutations; second, the expression of c-kit transcripts can be affected by mutations at the W locus; third, the tyrosine kinase activity associated with the protein encoded by c-kit is functionally impaired in mast cells derived from mutant W/Wv mice; and fourth, rearrangements within the c-kit gene have been reported in two W mutant alleles. These observations suggest that the dominant phenotype associated with W mutations results from loss-of-function alterations that affect the receptor tyrosine kinase encoded by c-kit. The demonstration that the W locus encodes a transmembrane growth factor receptor provides a molecular basis for understanding the intrinsic haemopoietic defect in W mutant mice and the role that this cellular proto-oncogene plays in haemopoiesis and other developmental processes.

Animals↗
PubMed1990

The selection of thin epithelial layers: a method for single cell preparations of very small biopsies from the vocal cords.

Precancerous lesions in biopsy material very rarely contain more than a thin epithelial layer of atypical cells overlaying stromal parts. This makes it difficult to produce cell monolayers for cytometry from archival material and necessitates a technique which excludes the stromal areas. We have developed a method by which it is possible to separate epithelial layers from the stroma with a thickness of 100-200 microns, using fluorescence microscopy and dissection under a stereo microscope. The stroma can be used as an internal reference in IOD measurements. Our method insures maximum control when dealing with very small lesions of interest (down to 0.02 mm2) that have to be separated from the rest of the biopsy. The method has been applied to normal, dysplastic and cancerous epithelial parts of biopsies of the vocal chords.

Biopsy↗
PubMed1989

Characterization of the morphological properties of welding fume particles by transmission electron microscopy and digital image analysis.

The morphological characteristics of welding fume particles have been determined using transmission electron microscopy (TEM) and automatic image analysis (AIA). Two personal samples and one background sample were collected using a new, easy to handle sampling method, during tungsten inert gas (TIG) and manual metal arc (MMA) welding on Inconel in the same shop. The collection method gave samples which were suitable for TEM and AIA. Electron micrographs were taken in a transmission electron microscope and further analyzed using an image analysis unit. Aggregates composed of many individual particles were analyzed both for the parameters of the aggregate and for the parameters of the individual particles by using an algorithm based on a grain boundary reconstruction technique. The morphological parameters allowed the welding fume's particulate matter to be divided into three types - here called small, medium, and large - with a somewhat unclear distinction between medium and large. Medium and large particles occur either as individual particles or as clusters of approximately spherical particles with average diameters of 0.07 and 0.15 microm, respectively. Small particles occur almost exclusively as long chains or lace-like structures of aggregates of particles, often in the range of 5-10 microm. The aggregates have an average projected area of 2.6 x 10-3 microm2 and are composed of several hundred individual particles.

Air Pollutants↗
PubMed1989

Early changes of intracranial pressure, perfusion pressure, and blood flow after acute head injury. Part 1: An experimental study of the underlying pathophysiology.

The present study examines intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral circulation immediately after experimental head injury in an animal model. The underlying systemic hemodynamic changes were also observed. To produce a standardized head injury, a fluid-percussion device was applied to the dura at the midline of 10 piglets. Seven other nontraumatized animals served as a control group. Hemodynamic parameters as well as ICP and CPP were recorded on-line, one value every 1.4 seconds. Cerebral blood flow (CBF) and cerebral vascular resistance (CVR) were measured three times using a microsphere technique. Immediately after head injury, the traumatized animals showed a sudden increase in ICP, with a maximum of 40 torr at 3 to 5 minutes, while there was a pronounced decrease in CPP from 85 to 40 torr. The CBF in the various brain areas fell from 55 to 22 ml/min/100 gm within 5 minutes after the impact, and CVR increased to 300% of control values within 90 minutes. The findings of this study demonstrated that cerebral circulation is critically jeopardized within a few minutes after trauma. This, in combination with a subsequent increase in CVR, makes the early development of ischemic brain damage very likely. In traumatized patients, treatment prior to hospital admission must therefore be directed at prevention of this fatal course.

Acute Disease↗
PubMed1989

Characterization of chromatin structure by image analysis--a method for the assessment of changes in chromatin organization.

This paper describes an image analysis technique for the assessment of changes in chromatin organization in ultrathin tissue sections. Transmission electron micrographs of tissue sections were analyzed by a SEM-IPS image processing unit (Kontron) at a total magnification of 7,500. The boundaries of each nucleus and each nucleolus were defined interactively, and the grey level threshold between heterochromatin and euchromatin was determined. The grey level distribution and the total area of each nucleus was measured. In addition, the total area, number, and individual areas of heterochromatin particles and nuclei were measured. Based on these measurements, a number of different variables have been defined, and several of these have proved to discriminate between normal and malignant cells.

Animals↗
PubMed1988

Modification of surfactant metabolizing cells in rat lung by clofibrate, a hypolipidemic peroxisome proliferating agent. Evidence to suggest that clofibrate influences pulmonary surfactant metabolism.

The influence of clofibrate (ethyl-alpha-p-chlorophenoxy-isobutyrate), a hypolipidemic peroxisome proliferating agent, has been tested on the lungs of adult male rats. Drug administration for 7 days caused structural changes in two types of lung cells, both of which are involved in the metabolism of the pulmonary surfactant. By light microscopy the prominent features were the presence of enlarged type II alveolar epithelial cells and foamy intraalveolar macrophages. Compared with controls, type II cells in treated rats apparently contained more numerous surfactant-containing lamellar bodies, as visualized in semi-thin sections of Epon-embedded tissue. This difference was quantified morphometrically by light microscopy: the number of lamellar bodies was estimated as the profile number per individual type II alveolar cell, transsected at its nucleus. Clofibrate administration for 7 days resulted in a significant increase in the number of the lamellar inclusions. In contrast the number of type II alveolar cells per area of lung remained unchanged. There was no evidence of atelectasis or inflammatory infiltration in the drug-treated lungs, a finding confirmed in sections of perfusion-fixed, paraffin-embedded whole lung-lobes. By electron microscopy the lamellar inclusion bodies in the type II alveolar cells in treated rats, apart from being more numerous and sometimes smaller, were morphologically identical to those in controls. The vacuolated alveolar macrophages seen in treated rats also contained various lamellar phospholipid inclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Keratin and involucrin in preneoplastic and neoplastic lesions. Distribution in the nasal mucosa of nickel workers.

Nasal mucosal biopsy specimens encompassing normal and pathological epithelia were obtained from nickel workers, a population with an increased incidence of carcinomas of the respiratory tract. The immunohistochemical detection of keratins was carried out using monoclonal antibodies AE1 and AE3. The antibody AE1 stained only the basal cells of normal mucociliary epithelium. Regular metaplasias showed an increased stain with AE3; all layers of the surface epithelium were stained. The dysplastic and neoplastic lesions exhibited an extraordinary increase in the staining patterns with AE3 and to a lesser extent with AE1. Involucrin, which was absent from the normal pseudostratified epithelium, appeared in all metaplastic-dysplastic lesions and in keratinized areas of carcinomas. The combined detection of keratins and involucrin proved useful in detecting the degree of maturity and differentiation of preneoplastic and neoplastic lesions of the nasal mucosa.

Antibodies, Monoclonal↗