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Fluorescence lifetime study of two probes abbreviated as Py-Htelom-Py and Py-TBA-Py, carrying pyrene moieties at both termini and sequences of Human telomere and Thrombin Binding Aptamer, respectively are reported. The effect of potassium ion on the photophysical processes was examined in order to elucidate factors that facilitate the production of excimer emission. Emission kinetics data indicated that the relative orientation of pyrene and neighboring nucleobase (guanine, adenine, thymine) plays a crucial role in determining both the rate of electron-transfer quenching of pyrene excited state and the efficiency of excimer emission.

A3 was generated as an antibody recognizing somatic stem cells in rat tissues. We investigated the distribution of A3-positive cells in developing rat hair follicles by immunolabeling. A3-positive cells began to be seen in the hair germ and peg in fetuses and neonates; the positive cells were epithelial cells above basal cells. Furthermore, A3-positive cells were seen in the outer root sheath adjacent to the bulge in mature hair follicles. Double immunofluorescence revealed that these A3- positive epithelial cells reacted to E-cadherin (for all epithelial elements) but not to CK15 (for basal cells/epithelial stem cells) or to nestin (for stem cells), indicating that A3-positive epithelial cells are suprabasal cells in the developing epidermic hair follicle. Additionally, spindle-shaped mesenchymal cells surrounding the hair peg and mature hair follicle reacted to A3; in double immunofluorescence, the A3-positive cells were located outside collagen type IV-positive glassy membrane, and reacted to vimentin (for mesenchmal cells), Thy-1 (for immature mesenchymal cells), CD34 (for stem cells) and nestin, but not to α- smooth muscle actin (for myofibroblasts); the positive cells were regarded as immature mesenchymal cells with stem cell nature in the connective tissue sheath of developing hair follicles. A3-positive epithelial and mesenchymal cells did not show proliferating activity. Collectively, it is considered that A3-positive cells seen in developing rat hair follicles may be quiescent postprogenitor cells with the potential to differentiate into either highly-differentiated epithelial or mesenchymal cells. A3 would become a useful antibody to know the kinetics of rat hair follicle-constituting cells.

To study potential toxic effects of long-term (8 h) inhaled prostacyclin (PGI2) on respiratory tract tissues.In a prospective, randomized order, either PGI2 (n =7) or normal saline (n = 7) was aerosolized during a time period of 8 h in healthy lambs.Institute for Surgical Research of the Ludwig-Maximilians University of Munich.14 health, anesthetized, ventilated lambs.All animals were endotracheally intubated followed by tracheotomy. PGI2 solution or normal saline was administered with a jet nebulizer (delivery rate 4-10 ml/h; mass median diameter of aerosol particles 3.1 microns).Histomorphological changes after 8-h inhalation of PGI2 solution were compared to those after 8-h inhalation of normal saline. Tracheal and bronchoalveolar tissues were examined by light and electron microscopy in order to assess tissue damage induced by inhaled PGI2. Pathological changes were ranked by a blinded observer following a graduation system ranging from "absence of pathological changes" to "maximal pathological changes". Abnormalities were restricted to the trachea (focal flattening of the epithelium, loss of cilia, slight inflammatory cell infiltration) and alveolar tissue (focal alveolar septal thickening with slight inflammatory cell infiltration), but no statistically significant differences between the PGI2 and control groups were encountered.Our findings indicate the absence of PGI2 aerosol-related respiratory tissue damage after 8-h inhalation of PGI2.

An effective therapy which assists the elimination of the residual chlorinated compounds in Yusho patients has still not been established. To determine the behavior of polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in patients 20 years since the occurrence of Yusho disease, the concentrations of PCBs and PCDFs in the blood, subcutaneous adipose tissue and stools were investigated in six patients with typical symptoms of Yusho disease. The daily excretion levels of 2,3,4,7,8‐penta‐chlorodibenzofuran (PnCDF), and 1,2,3,4,7,8‐ and 1,2,3,6,7,8‐hexachlorodibenzofurans (HxCDFs) into the stools of Yusho patients were 200 to 1380pg, and 190 to 1590pg, respectively. Similarly, PCBs were excreted at levels of 320 to 1370 ng per day, into the stools. The amounts of PnCDF and HxCDFs excreted into the stool per day was correlated to the levels of those chemicals in the blood and subcutaneous adipose tissue. The daily levels of PnCDF and HxCDFs excreted into the stool were comparable with th...

Pulmonary changes of 153 male Wistar rats were examined histopathologically after continuous exposure to cadmium oxide dust (CdO) at concentrations of 0, 30 or 90 Myg Cd/cubic meter for a maximum period of 18 months. In the 90 Myg-exposure group, the exposure was terminated at 7 months due to an increase of mortality. Six to 8 animals of each group were sacrificed at 6 months and - with the exception of the 90 Myg-exposure group - at 18 months (sequential sacrifice study). Subsequent to the inhalation period, remaining animals were kept unexposed until the termination of the experiment at 31 months (basic study). At 6 months, animals of both exposure groups inflammatory reactions in the alveolar region. Bronchiolo-alveolar hyperplasia was also observed. In the 90 My g-exposure group the changes were more severe than in the 30 Myg-exposure group. At 18 months, abnormal proliferation of epithelia (nodular formation of mucus-secreting cells, basophilic foci of cuboidal epithelia and adeno matous proliferation of epithelia) occured in the 30 Myg-exposure group in association with the changes observed at 6 months. In the basic study primary lung tumors developed in 72 % of the 30 My g-exposure group and in 31 % of the 90 My g-exposure group. The tumor incidence is obviously dependent on the duration of exposure, which was much shorter in the 90 My g-exposure group. The lung tumors were classified as bronchiolo-alveolar adenomas and adenocarcinomas, benign and malignant squamous cell tumors, and an adenosquamous carcinoma. The types of tumors observed in this experiment were identical to those in duced in a previous experiment using CdCl sub 2 and in a parallel experiment using CdSO sub 4, CdS and CdCl sub 2. The findings of this study suggest that progressive prolifertion of bronchiolo-alveolar epithelia can lead to the development of lung tumors in rats exposed to CdO.

In parallel inhalation and intraperitoneal injection (i.p.) experiments with rats, the glass fibre JM 104, Tempstran 475, exemplifying a very thin and durable man-made mineral fibre (MMMF), was compared with crocidolite (South Africa) and chrysosotile (California. Calidria RG 144). Aerosol concentrations were 2.2-6 mg m(-3). Exposures lasted 1 yr. No significant tumour rate was found in the inhalation test nor from an exposure combination of 100 ppm SO2 and glass fibres. In 74% of the animals exposed to crocidolite bronchiolo-alveolar hyperplasia was detected. Intraperitoneal injection of 0.5 mg of the three different fibre types showed a tumour tate of 17% for glass fibre JM 104, 55% for crocidolite and only 6% for Calidria chrysotile. Calidria chrysotile seems to be much less persitent than other chrysotile samples. The long persistence of JM 104/475 in the lung (half-time of lung clearance about 600 days) and the carcinogenic effects of these fibres after intraperitoneal injection i ndicate that after inhalation of thin (smaller than 1 mym), long and durable MMMF the suspicion of a carcinogenic potency of these fibres is still well-founded.

Lung cancers were induced in inbred W rats by cadmium chloride aerosols. For 18 months, 120 male W rats were continuously exposed to cadmium chloride aerosols with cadmium (Cd) concentrations of 12.5, 25, and 50 myg/cubic meter, respectively. For the same period of time, 41 rats were kept in filtered air; these rats served as the control group. The survivors were killed 13 months after the end of the inhalation experiments. Histopathologic examination revealed a dose-dependent incidence of primary lung carcinoms of the following types: adenocarcinomas, epidermoid (squamous cell) carcinomas, combined epidermoid carcinomas and adenocarcinomas, and mucoepidermoid carcinomas. The incidence of lung carcinomas was 71.4% in the group exposed to 50 myg Cd/cubic meter, 52.6% in the group exposed to 25 myg Cd/cubic meter, and 15.4% in the group exposed to 12.5 myg Cd/cubic meter. None of the controls developed lung carcinomas. At the end of the experiment, the remaining Cd concentrations in the lungs were relatively high, almost at the same level as those in the livers. (ITA)

Drei als relativ inert angesehene Staeube wurden im Hinblick auf moegliche Schadwirkung auf die Lunge untersucht. Es wurde ueberprueft, ob sich diese Stoffe einheitlich verhalten oder ob spezifische Stoffeigenschaften wie z.B. die Dichte zu beruecksichtigen sind. Als "nicht-toxische" Staeube werden Titandioxid (Rutil), PVC-Pulver und Eisenstaub mit den Dichten 4.3, 1.3 und 8 g/cbm ausgewaehlt. Die Aerosolkonzentrationen lagen jeweils bei 3.2, 8 und 20 mg/cbm. Bei der hoechsten Staubkonzentration war nach 8-monatiger Exposition die Lungenclearance der PVC-Partikeln etwa um den Faktor 3.3 verlangsamt; bei der Clearance der radioaktiv markierten Testpartikeln 59Fe2O3 und 85Sr-Polystyrol ergaben sich entsprechende Verlangsamungen um die Faktoren 1.4 und 3.2. Histopathologisch wurde nach TiO2- und PVC-Staubinhalation ausser der Ansammlung von partikelbeladenen Makrophagen eine leichte Septenverdickung beobachtet. Bei der hoechsten PVC-Konzentration trat eine leichte interstitielle Entzuendu ng auf. Diese Ergebnisse zeigen, dass die Wirkung der untersuchten Staeube vor allem auf die alveolaere Clearance sehr unterschiedlich ist. Eine Ueberpruefung des Allgemeinen Staubgrenzwertes erscheint nach diesen Ergebnissen angebracht. (ITA)

A subchronic inhalation study, using SPF, F-344 rats, was conducted for 6 hr/da, 5 da/wk for 13 weeks. The special test toner was enriched about 10-fold, respirably (ACGIH), relative to product. Nominal exposure levels were 0, 1.0, 4.0, 16.0 and 64 mg/cubic meter (0, 0.35, 1.4, 5.6 and 22.4 mg/cubic meter, respirable). The exposures were well-tolerated, with no unscheduled deaths. Significant findings were restricted to the high exposure groups. The MTD (pulmonary) was determined relative to a defined Maximum Functionally Tolerated Dose (MFTD). At the lower exposures, clearance measurements of toner and a spike of iron oxide (Fe-59) were essentially unchanged from controls. At 16 mg/cubic meter, slight effects were observed. At 64 mg/cubic meter, no appreciable toner clearance occured after 60 da exposure. The MFTD was deemed to be exceeded at 64 mg/cubic meter and 16 mg/cubic meter was chosen for the chronic study high concentration. (ITA)

SPF F-344 rats were exposed to a special test toner by the inhalation route. The animals were kept for an additional six weeks in filtered air. Surviving animals were sacrificed at 25.5 months after start of exposure. Life-span and causes of death were independent of treatment and in accordance with published values. No evidence for systemic toxicity or any upper-respiratory system effects were found in the toner exposed groups. The incidence of lung tumors was comparable in the control, 3 toner and Ti02-exposed groups. An incidence of 18% combined benign and malignant tumors was observed in the quartz treated rats. A slight to moderate degree of fibrosis was observed at the toner high exposure level in all animals, while a very slight degree of fibrosis was noted in 20% of the animals at the toner middle exposure level. The fibrogenic potency of the test toner was calculated to be comparable to Ti02. No pulmonary changes were seen at the toner low and environmentally most relevant exp osure level.

Syrischen Goldhamstern wurden im chronischen Versuch verschiedene nickelhaltige Staeube 12 mal ueber einen Zeitraum von 170 Tagen intratracheal instilliert. Die kumulative Staubdosis betrug bei Nickelpulver 9,6 mg, bei Ni3S2 1.2 mg, bei Pentlandit 36 mg, bei Cr-Ni-Stahlschleifstaub (18/10 Cr-Ni-Stahl) 37 und 108 mg und bei einem Cr-Stahlschleifstaub 108 mg. Die Halbwertzeiten fuer die Nickelclearance der Lunge wurden fuer Nickelpulver mit 152 Tagen, bei Ni3S2 mit weniger als 14 Tagen, bei Pentlandit mit 120 Tagen und bei Cr-Ni-Stahlschleifstaub mit etwa 450 Tagen abgeschaetzt. Der Medianwert der Lebenszeit der Versuchstiere lag bei allen Gruppen ueber 18 Monaten und erfuellt damit den Richtwert fuer Kanzerogenitaetsstudien beim Hamster. Statistisch signifikant erhoehte Tumorraten der Lunge wurden nicht beobachtet. Nach Behandlung mit Nickelpulver wurden 1 Lungentumor und vereinzelt Metaplasien bei den 56 behandelten Hamstern nachgewiesen. Trotz extrem hoher Dosierung wurden nach Instil lation von Pentlandit nur 1 Lungentumor und nach Behandlung mit Chromnickel-Stahlstaub kein behandlungsbedingter Tumor beobachtet. (ITA)

Es wurde ein Verfahren ausgearbeitet und ein Geraet zur Messung von Faseremissionen aus verwitterten und kondierten Asbestzement-Produkten entwickelt. Mit Hilfe dieses Verfahrens werden Emissionen und Immissionen faseriger Staeube an Bauten mit verschiedenen Daechern und Fassaden gemessen. Die Emissionen lagen im Bereich von 10 hoch 6 bis 10 hoch 8 Fasern/qm/h und die Immissionen waren 50-1000 Fasern/cbm. (IUCT)

A long-term exposure study with hamsters, mice and rats inhaling filtered and unfiltered diesel engine exhaust was carried out to investigate effects of chronic toxicity and, predominantly, carcinogenicity in the respiratory tract. The level of diesel exhaust in the exposure chambers corresponded to a concentration close to 4 mg m over the minus 3 power in the unfiltered diesel exhaust. Satellite groups of animals were additionally treated with BaP, DBahA or nitrosamines in order to check for syncarcinogenic effects. In hamsters and rats, alveolar lung clearance and mechanical lung function tests as well as biochemical and cytological measurements in lung lavage fluids showed significant changes only after exposure to unfiltered diesel exhaust and, predominantly, in rats. No lung tumors were found in hamsters. Spontaneous tumor rates occured in mice and both types of diesel exhaust increased the incidence of adenocarcinomas in the lungs. In rats, only the unfiltered diesel exhaust caus ed a lung tumor incidence. It amounted to 16% with no tumors in the controls. The heavy load of particulate matter in the lungs of rats was caused by an exposure-related impairment of the alveolar lung clearance and may have been instrumental in the induction of squamous cell tumors. However, an effect of particle-associated PAH cannot be excluded. Syncarcinogenic effects of diesel exhaust after initial carcinogen treatment were found only in the respiratory tract of rats.