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Biomedical subjects

M Emura

Publications and source records attributed to M Emura.

At least 55 records · Page 3Linked to original sources

[Correlation of CT and pathologic findings of pulmonary lymphangioleiomyomatosis].

The X-ray CT findings of two cases of pulmonary lymphangioleiomyomatosis were reported. The correlation between high-resolution CT findings and inflated biopsy specimens was studied. The X-ray CT findings are 1) multiple low attenuation areas, 2) diffuse areas of slightly increased density and 3) irregular enlargement of pulmonary vascular images. Each low attenuation are turned out to correspond to emphysematous lesions. Slightly increased densities on CT images seemed to be caused by a summation of many small nodules of a proliferation of smooth muscle cells located in the wall of respiratory bronchioles and alveolar ducts, with or without intraalveolar hemosiderosis. Some nodular lesions in bronchiolar walls were so close to neighboring vessels that they could not be separated from vascular images on CT, so peripheral vascular images were irregularly thickened. X-ray CT reflected more actual pathological findings than routine chest radiographs. As low attenuation areas on CT images have been reported to be representative of pulmonary emphysema, it is thought that the above CT findings must be differentiated from those of pulmonary emphysema. While pulmonary vascular images were thin and stretched on the CT in patients with emphysema, they were irregularly thickened on the CT of patients with LAM. Furthermore, while CT of emphysema often revealed overinflation or decreased density, diffuse areas of slightly increased density were never found in emphysema.

Adult↗

Spontaneous lesions in the respiratory epithelium of the Syrian golden hamster as seen by scanning electron microscopy.

The respiratory epithelium of 8, 12.5 and 17.5-month-old Syrian golden hamsters was investigated by scanning electron microscopy (SEM) and routine light microscopy (LM) of paraplast sections. In selected cases, SEM-specimens were embedded in Epon after SEM evaluation. The samples were cut in semithin sections and examined by light microscopy. The density of ciliated cells in the respiratory epithelium differs from hamster to hamster. Care must, therefore, be taken when diagnosing simple metaplasia by SEM alone unless a sufficient number of damaged cilia are present. Only 1 animal (8 months old) exhibited squamous metaplasia of the tracheal mucosa. However, surface polymorphism resembling squamous metaplasia was seen in almost every specimen. The polymorphism was caused by either submucosal calcifications or by cystic changes of hypertrophic submucosal glands. In addition, variously formed aggregations of mucus were seen protruding from duct openings of hypertrophic submucosal glands. To avoid false positive or negative diagnosis which can occur when screening is done by SEM alone, light-microscopical examination of sections cut from SEM identified lesions appears necessary.

Animals↗

[Spontaneous immunoglobulin secreting cells in idiopathic usual interstitial pneumonia].

Abundant evidence suggests that activation of B lymphocytes and formation of immune complexes play important roles in the pathogenesis of idiopathic pulmonary fibrosis. We investigated the level of B lymphocyte activation in patients with idiopathic UIP (n = 10, all were biopsy proven cases), for the purpose of evaluating its role. In order to determine the level of B lymphocyte activation, the number of spontaneous immunoglobulin secreting cells in blood was counted by using reverse hemolytic plaque assay. The number of IgA and IgG secreting cells significantly increased in patients with idiopathic UIP when compared with those in healthy controls (n = 8). The number of IgG secreting cells also significantly increased in patients with IP-CVD, but no significant increase in the number of Ig secreting cells could be detected in patients with pulmonary emphysema, diffuse panbronchiolitis or sarcoidosis. The study of cell surface markers revealed significant increase of CD21 (B2 and OKB7) positive cells in patients with idiopathic UIP. CD21 positive cells were immature B lymphocytes. These results suggest that increase of resting B lymphocytes and immunoglobulin secreting cells occurred and that the differentiation of B lymphocytes may be accelerated in idiopathic UIP. Furthermore, there is the possibility that soluble factors produced by T lymphocytes influenced the function of B lymphocytes in our experiment.

Aged↗

[Mechanism of activation of B lymphocytes in idiopathic UIP: evaluation of BCGF and BCDF-production from blood T lymphocytes].

The activation of B lymphocytes and formation of immune complexes were suggested to play important roles in the pathogenesis of idiopathic UIP. To investigate the mechanism of the activation of B lymphocytes, we studied the production of B cell growth factor (BCGF) and B cell differentiation factor (BCDF) in patients with idiopathic UIP and those with IP-CVD, in comparison with healthy controls. Culture supernatants of peripheral blood mononuclear cells from patients with idiopathic UIP induced more IgM- and IgA-production than those from healthy controls, indicating a higher production of BCDF. Culture supernatants of peripheral blood mononuclear cells from patients with idiopathic UIP did not induce higher proliferation of B lymphocytes than those from healthy controls, indicating that production of BCGF was not enhanced in the patients. Increase of production of BCGF and BCDF from patients with IP-CVD was not observed. From these results, it was suggested that T lymphocytes that release lymphokines like BCDF are activated in patients with idiopathic UIP, but not in those with IP-CVD, and that the process of activation of B lymphocytes might be different between these fibrotic diseases.

Aged↗

Possible role of genetic predisposition in multigeneration carcinogenesis.

A peculiar phenomenon in experimental transplacental carcinogenesis is that in certain animal species or strains, and with certain types of carcinogens, a tumorigenic risk is observed not only in the F1 generation but also in subsequent F2 and even F3 generations when only the P generation has been exposed to a carcinogen. Additionally, in many cases, specific types of organs tend to be involved. For example, lung tumours are most common in P, F1 and F2 generations of Swiss, ICR, MA and CD-1 mice after exposure of the pregnant P generation to 7,12-dimethylbenz[a]anthracene (DMBA), urethane, DMBA and diethylstilboestrol, respectively. In such mice, the mammary glands, lymphatic tissues and ovaries are also frequently involved. Recently, two-stage tumorigenesis in skin with a phorbol acetate as promoter was transmitted to F2 descendants born of F1 SHR mice exposed transplacentally to DMBA. In WKA, BD IV and BD VI rats, nervous tissues seem to be prone to tumour development in F2 and/or F3 descendants born of F1 exposed transplacentally to N-methyl-N-nitrosourethane, N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea (ENU), respectively. In F344 strain rats, however, two-stage genesis of preneoplastic foci in the liver with 2-acetylaminofluorene (2-AAF) as the promoter failed to be transmitted to F2 and F3 generations from the F1 generation, which developed the preneoplastic hepatocellular foci after prenatal exposure to ENU followed by postnatal promotion by 2-AAF. Our own recent experiments with Syrian hamsters, in which multigeneration transmission of organ-specific (tracheal epithelium) tumorigenicity of N-nitrosodiethylamine was investigated, have also failed to show this phenomenon in F2 and F3 descendants. However, various field studies on pedigrees with frequently affected siblings indicate the existence of a heritable predisposition to tumour development over more than two generations. The organs involved include ovaries, mammary glands, stomach, lympho- and myelogenic systems, skin and nervous system. Interestingly, little or no such evidence has been found in the liver, respiratory tract (except for the nasopharyngeal region) or urinary tract. In the light of these experimental and human observations, the authors are currently inclined to hypothesize a heritable predisposition to tumour development in organs specific to animal species and strains, or certain families in human cases, for explaining the mechanisms underlying multigeneration transmission of chemical carcinogenicity.

Animals↗

[BALF cell findings in patients with BOOP, particularly in comparison with UIP].

It is possible to differentiate to some degree to bronchiolitis obliterans organizing pneumonia (BOOP) of unknown etiology from idiopathic usual interstitial pneumonia (UIP) on the basis of clinical symptoms, chest X-ray findings, pulmonary function test and blood gas findings, but in certain patients it can be difficult. Cell findings in bronchoalveolar lavage fluids (BALF) were compared between 8 patients with BOOP and 28 patients with UIP, both diagnosed histologically by open lung biopsy. Findings characteristic of BOOP included (1) an increase in the percentage of lymphocytes, (2) an increase in the percentage of eosinophils, and (3) a decrease in the OKT4+/OKT8+ ratio. These findings provide useful information in making a clinical diagnosis of BOOP and in evaluating proper steroid treatment in patients who unable to undergo open lung biopsy.

Adult↗

Regulation of growth and differentiation by vitamin A in a cloned fetal lung epithelial cell line cultured on collagen gel in hormone-supplemented medium.

Proliferative and differentiative responses to various doses of vitamin A (VA) were studied in the predifferentiated cells of a fetal Syrian hamster pulmonary epithelial line (M3E3/C3), which were cultured on a collagen gel in a hormone-supplemented medium. These predifferentiated cells possessed well-developed endoplasmic reticulum (ER) and Golgi apparatus. At VA doses higher than 8 micrograms/ml, periodic acid Schiff and slightly alcian blue positive mucuslike granules were produced, which were also detectable electron microscopically. These mucuslike products were rich in sialic acid and resembled quite well those from primary cultures of tracheal epithelial cells of Syrian hamster sucklings when analyzed by column chromatography on various types of gel. At all VA doses studied (2.4, 8, 24 micrograms/ml), cells grew exponentially with an average population doubling time of around 74 h, whereas in the absence of VA they had a linear growth rate and a population doubling time of 158 h between Days 4 and 11. The uptake of [3H]glucosamine into the whole cell homogenates showed a peak at Day 8, irrespective of VA doses (0 to 24 micrograms/ml), and at the highest VA dose (24 micrograms/ml) it exceeded by twofold the control (0 microgram/ml) level. At the same time, [14C]thymidine demonstrated a high peak of uptake on Day 8 at 8 and 24 micrograms/ml VA. There was virtually no difference between 0 and 2.4 micrograms/ml VA, with both doses yielding much lower peaks. Based on the results currently presented and previously reported, three successive stages were hypothesized for the mucous differentiation processes in M3E3/C3. The process from the first undifferentiated stage to the second predifferentiated stage with well-developed ER and Golgi apparatus requires both collagen gels and hormones. Differentiation from the second stage to the third secretory stage with mucous granules is stimulated by VA. These observations indicate that the cell line M3E3/C3 could provide a new system for investigating the mechanisms of mucus differentiation by VA.

Animals↗

Toxicity and chromosomal damage in fetal Syrian hamster and human pulmonary epithelial cells.

In order to test the hypothesis that human chromosomes are more stable than those of rodents, we compared the fetal human and Syrian hamster pulmonary epithelial cell lines for their sensitivity to the induction of cytotoxicity (CT), chromosomal aberrations (CAs) and sister-chromatid exchanges (SCEs). One day after plating, the cells were exposed for 2 h to various doses of ENU dissolved in an exposure medium consisting of McIlvaine buffer, RPMI 1640, and bovine serum albumin. CAs and SCEs were examined in 24-64 post-exposure hours by the standard methods, while CT was determined by cell counts. The frequency of CAs (particularly chromatid exchanges) and that of SCEs showed clear dose dependency and was remarkably higher in the hamster than in the human cells. CT determined in 1 week of post-exposure incubation showed a similar dose response for both cell lines with sharply declining regressions. These results suggest that human chromosomes are indeed more resistant to ENU-inducible aberrations than hamster chromosomes and that CT may not always be directly associated with chromosomal damage.

Animals↗

Failure to transmit diethylnitrosamine tumorigenicity from transplacentally exposed F1 generation Syrian hamsters to the respiratory tract of F2 and F3 generations.

A multigeneration study with four successive generations of Syrian hamsters was conducted to determine whether a single s.c. injection of different doses of diethylnitrosamine (DEN) (1.25, 2.5, 5, 10, and 20 mg/kg body weight) on day 15 of pregnancy induces respiratory tract tumors not only in the treated P generation mothers and their F1 progeny but also in F2 and F3 generations. In this study, the P generation mothers only were given a single injection of DEN during the period of gestation. Fifty-six % of the 36 DEN-treated mothers and 52% of their F1 generation offspring (total, 233 animals) developed neoplasms in the respiratory tract. A single respiratory tract tumor was found in one DEN-unexposed F1 generation control hamster as well as in one F2 generation animal (total, 209 animals) descended from DEN-exposed P generation. Both tumors were considered to have arisen spontaneously. No respiratory tract tumors were observed in the F3 generation (total, 160 animals) descended from a DEN-exposed P generation. Thus our results indicate that the vertical transmission of the tumorigenic effect of DEN in Syrian hamsters is limited to one generation and does not persist in the F2 and F3 generations.

Animals↗

Predisposition of cloned fetal hamster lung epithelial cells to transformation by a precarcinogen, benzo(a)pyrene, using growth hormone supplementation and collagen gel substratum.

A cloned fetal Syrian hamster lung epithelial cell line (M3E3/C3) was used to compare the influence of two different culture conditions on the degree of cellular differentiation and susceptibility of the cells to undergo malignant transformation by a precarcinogen, benzo(a)pyrene. Conventional conditions consisted of growth medium containing Roswell Park Memorial Institute Medium 1640, pyruvate, and fetal bovine serum and a substratum of plastic. Complex conditions comprised the growth medium supplemented with insulin, hydrocortisone, estradiol, epidermal growth factor, transferrin, and cholera toxin and a substratum of collagen gel. Under the complex culture conditions, there was extensive development of endoplasmic reticulum and Golgi vesicles, whereas under conventional conditions these organelles were only minimally developed. This was correlated with 1.5-1.8 times enhancement of ethoxycoumarin deethylase and reduced nicotinamide adenine dinucleotide phosphate-dependent cytochrome c reductase activities. Decomposition of added benz(a)anthracene into water-soluble compounds increased with the period of incubation and reached about 40% of initial benz(a)anthracene (50 micrograms/10 ml/flask) at 48 h under the complex conditions, whereas under the conventional conditions only less than 4% decomposition occurred. Benzo(a)pyrene in the dose range 2-8 micrograms/ml was strongly cytotoxic and caused significant anchorage independent transformation only under complex culture conditions. Transformed cells produced tumors in two of four hamsters during 8 months following s.c. injection within 48 h of birth. These results suggest that the complex culture conditions predisposed the cloned fetal epithelial cells to malignant transformation by benzo(a)pyrene through stimulation of cellular differentiation and development of enzyme systems capable of activating it metabolically.

Animals↗

Development of intracytoplasmic lumina in diethylnitrosamine-induced tracheal papillomas of Syrian golden hamster. A light and electron microscopical study.

Tracheal papillomas in the Syrian golden hamster were induced with diethylnitrosamine (DEN). Intracytoplasmic lumina filled with mucus were studied by light and electron microscopy. The sequence of lumen genesis is described ultrastructurally. Mucus substances in the center of intracytoplasmic lumen are presumed to be condensations of cell coat macromolecules. The intracytoplasmic lumen is discussed as a common feature of the adenoid component in epithelial neoplasms.

Animals↗

Comparison of chrysene metabolism in epithelial human bronchial and Syrian hamster lung cells.

Chrysene is metabolized to 1-, 2-, 3-, and 4-hydroxychrysene and trans-1,2- as well as trans-3,4-dihydroxydihydrochrysene in human and Syrian hamster epithelial lung cells as indicated by GC/MS analysis, whereas K-region oxidation is at most a very minor pathway. Cells of a permanent clonal line of fetal hamster lung metabolized 97% of the chrysene whereas fetal human bronchial epithelial cells converted 24% of the substrate within 8 days incubation. In human cells oxidation at the 3,4-position predominates, whereas oxidation at the 1,2-position is the major pathway in hamster cells. Indication for a bay-region oxidation of chrysene in hamster cells has been obtained.

Animals↗

Autophagic mechanisms in diethylnitrosamine-induced tracheal papillomas of Syrian golden hamster.

Treatment with diethylnitrosamine induced tracheal papillomas in the Syrian golden hamster. Enlarged lysosomes (EL) occurred in a particular type of cells situated at the periphery of tumor lobules. The differentiated phenotype of these cells in secretory in nature. As to the significance of EL occurrence, two possibilities are considered: 1) EL formation is a part of disposal mechanisms after the autophagocytosis of undischarged secretory products by secondary lysosomes and 2) ELs are indicative of sublethal injury to cells of the outermost layer of tracheal papillomas.

Animals↗

Ciliated cells in diethylnitrosamine-induced tracheal papillary tumors of Syrian golden hamster.

Tracheal papillomas in the Syrian golden hamster were induced by diethylnitrosamine. The occurrence of ciliated cells was quantitatively analysed on 134 step sectioned tumors by light microscopy and qualitatively by transmission (23 tumors) and scanning electron microscopy (24 tumors). Ciliated cells were observed in 40% of all tumors, mostly at the basal part of the tumor opposite the normal epithelium or in the folds between tumor lobes. In 6% of all tumors ciliated cells were located on the apical luminal surface of tumors. Since ciliogenesis was observed only in 2 tumors, we presume that most of the ciliated cells in papillary tumors were not developed from the neoplastic cells through de novo ciliogenesis, but were preexisting ciliated cells which migrated into tumor compartments during the neoplastic growth.

Animals↗

Growth stimulation by retinol apparently independent of EGF receptor.

A respiratory epithelial cell line M3E3/C3, derived from fetal Syrian hamster lung, grew very slowly in RPMI 1640 medium with serum concentrations as low as 1.5%. Under these conditions the simultaneous action of epidermal growth factor (EGF) and vitamin A (retinol) was apparently a combination of growth enhancement attributable to each compound. Both compounds also affected the morphological growth pattern considerably. Binding experiments with 125I-labelled EGF showed that retinol had only a small (if any) reducing effect on the numbers of EGF receptors. Nonetheless, retinol showed a marked growth stimulation. As far as we are able to judge from most of the other reports that retinoids inhibited growth of cells and increased the EGF receptor number, this type of growth regulation is unusual.

Animals↗