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Biomedical subjects

R E Albert

Publications and source records attributed to R E Albert.

At least 73 records · Page 4Linked to original sources
PubMed1981

Coordination of mucociliary transport in human trachea and intrapulmonary airways.

A wide range of both mucus velocities in the trachea and rates of bronchial mucociliary clearance have been measured in humans. To investigate the coordination of mucociliary transport in the intrapulmonary and extrapulmonary airways, simultaneous measurements of tracheal mucus velocity and lung clearance were made in 22 healthy nonsmoking adults. Each subject inhaled several breaths of an iron oxide aerosol tagged with 99mTc. Measurements of retained activity in the right lung were made for 2.25 h with a pair of 5 x 2 in. NaI (T1) detectors. Tracheal mucociliary transport rates (TMTR) were measured with a probe containing six vertically aligned rectangular NaI (T1) detectors. The mean TMTR was 5.1 +/- 2.9 mm/min. The mean time for the first bolus to be detected on the multidetector probe (large airway transit time, LATT) was 52 +/- 24 min. At this time the percent cleared (Bi) was 24 +/- 15% and the rate of clearance (Bi) was 0.64 +/- 0.35%/min. The mean percent cleared within a 2-h interval (B120) was 51 +/- 22%. The TMTR was closely correlated with Bi and Bi with B120. The TMTR was also correlated to B120, but not closely correlated with LATT. It is suggesting that coordination of mucus transport throughout the airways of the lung represents the nonchallenged state and is responsible for the maintenance of normal bronchial toilet.

Adult↗
PubMed1981

The effects of irritant aerosols on mucus clearance from large and small conductive airways.

The effects of one hour exposures of healthy nonsmoking human volunteers to submicrometer H2SO4 droplets via nasal mask on tracheobronchial mucociliary particle clearance were studied using two different sized monodisperse gamma-tagged Fe2O3 test aerosols. The larger sized Fe2O3 aerosol, 7.5 micrometers AMAD, was deposited primarily in the larger bronchial airways, while the smaller 4 micrometers AMAD aerosol had a much greater fraction deposited in the smaller and more distal conductive airways. Thoracic retention of the Fe2O3 aerosols as a function of time after a brief inhalation was measured with external collimated radiation detectors. At the highest H2SO4 exposure, 1,000 micrograms/m3, there was a pronounced transient slowing of bronchial mucociliary clearance of both the 7.5 and 4 micrometers Fe2O3. On the other hand, at the lowest H2SO4 concentration, 100 micrograms/m3, there was a marked acceleration of the clearance of the 7.5 micrometers Fe2O3, but a slowing of the clearance of the 4 micrometers Fe2O3. Thus, submicrometer H2SO4, which deposits primarily in the distal airways, can slow mucociliary clearance in those airways. In the larger airways, where its deposition is minimal, the H2SO4 can, at the same time, accelerate mucus transport.

Adult↗
PubMed1981

Relationship of benign papillomas to cancer induction in mouse skin.

An analysis is presented for evaluating the potency of initiators, promoters, and carcinogens based on the number of tumors that occur as a function of dose and time when compounds are applied topically in an appropriate solvent to mouse skin. A given compound was tested as an initiator (a single dose followed by prolonged promotion), as a whole carcinogen (multiple applications for a prolonged period of time), and as a cocarcinogen (multiple applications for a prolonged period of time in combination with promotion). Compounds tested were 7,12 dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene (B(a)P), 4-nitroquinoline-1-oxide (4-NQO), and betapropriolactone (BPL). The results indicated that various types of papillomas were produced in proportion to the dose applied to DMBA, B(a)P, and BPL. Certain of these papillomas were nonregressible and progressed readily to carcinomas; others regressed and did not progress to cancer. Multiple doses of DMBA and B(a)P produced carcinomas without an antecedent papilloma stage. The latter cancers were produced in proportion to the 2nd or 3rd power of applied carcinogen dose and were accelerated strongly by concomitant action of a promoter. Certain nonregressible papillomas probably represent the first step in a two or three step progression to cancer, although cancers from papillomas occur in proportion to dose.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Age-dependent changes in prevalence, size and proliferation of arterial lesions in cockerels. II. Carcinogen-associated lesions.

Age-dependent changes were determined in the prevalence, frequency, size and proliferative activity of aortic lesions arising in cockerels injected weekly with the polycyclic hydrocarbon carcinogen, 7,12-dimethylbenz (a) anthracene (DMBA). Starting at 4 weeks of age, groups of 6 animals received weekly i.m. injections of DMBA (10 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO). Controls were injected with DMSO. Animals were sacrificed (DMSO). Controls were injected with DMSO. Animals were sacrificed at 4 week intervals between 8-20 weeks of age. Microscopic lesions were observed in the abdominal aortas of all animals regardless of age or treatment. At no time point were there statistically significant differences in the prevalence or frequency of lesions between DMBA-treated animals and age-matched controls. In addition, lesion areas were log-normally distributed in all groups. However, DMBA exposure elicited 2 sets of changes not seen in controls. Carcinogen treatment accelerated the time and rate of appearance of large lesions. Eight week old DMBA-treated animals displayed lesion sizes comparable to those seen in 20 week old controls. Continued exposure to DMBA resulted in sharp increases in lesion size up to 20 weeks of age. Between 12-20 weeks lesion size increased, in a nearly linear fashion, by 12X in DMBA-treated animals but only by 2X in controls. There also was a burst of lesion cell proliferation in cockerels after 12 weeks of DMBA treatment. No equivalent increase in proliferation was seen in lesion cells in controls or in medial cells of either experimental or control animals. These results demonstrate that chronic carcinogen exposure results in the accelerated development of pre-existing "spontaneous' lesions rather than the initiation of new lesions. In addition, the results indicate that lesions are not homogeneous regarding their response to proliferative stimuli. This suggests that within a lesion there may exist subpopulations of cells which are more capable of proliferating in response to DMBA, and presumably to other agents, than are the majority of lesion cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Inhibition of benz[a]pyrene-induced mammary carcinogenesis by retinyl acetate.

The administration of a 250-ppm retinyl acetate dietary supplement for various periods relative to intragastric administration of 50 mg benzo[a]pyrene (BP) significantly inhibited the induction of mammary cancers in virgin female inbred LEW/Mai rats. with day of BP administration taken as time 0, groups receiving the retinoid from weeks -2 to +1, +1 to +90, +20 to +90, and -2 to +90 showed a significant reduction in tumor response as compared to controls. The inhibition of carcinogenesis achieved by a +1 to +20 administration schedule was temporary; the tumor yield was suppressed initially but returned to control levels by week 60. Autoradiographic analysis of mammary glands from 50-day-old rats indicated that a 2-week exposure to supplemental retinyl acetate significantly reduced the mammary gland parenchymal cell labeling index in ductal, alveolar, and terminal end bud structures. Beginning the retinyl acetate supplement 1 week after the administration of BP significantly reduced the number of terminal ductal hyperplasias. The inhibition of carcinogenesis achieved by a short period of retinyl acetate administration before and during the period of carcinogen availability as well as the inhibition achieved by long-term postcarcinogen retinoid exposure may involve an antiproliferative effect on the rat mammary gland.

Animals↗
PubMed1980

Inhalation carcinogenicity of epichlorohydrin in noninbred Sprague-Dawley rats.

Inhalation exposure experiments with the direct-acting alkylating agent epichlorohydrin (ECH) were done on noninbred male Sprague-Dawley rats. Single 6-hour exposure to ECH and follow-up for 14 days showed the median lethal concentration to be about 360 ppm. Further inhalation experiments were done with 6-hour exposure 5 days/week. A short-term 30-exposure regimen with 100 ppm ECH produced malignant squamous cell carcinomas of the nasal cavity in 15 of 140 rats and respiratory tract papillomas in 3 rats. Among 100 rats, lifetime exposure to 30 ppm yielded 1 malignant squamous carcinoma of the nasal cavity plus 1 nasal papilloma. No nasal or respiratory tract tumors were produced by lifetime exposure of 100 rats to 10 ppm. As controls, 100 air-treated and 50 untreated rats were used. A dose-rate effect was observed for ECH inasmuch as 30-day exposure to 100 ppm (3,000 ppm-days) produced 15 cancers in comparison to the 1 cancer from the lifetime exposure to 30 ppm (8,700 ppm-days) and no cancers from lifetime exposure to 10 ppm (2,500 ppm-days).

Animals↗
PubMed1980

Deposition, retention, and clearance of inhaled particles.

The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from the alveolar region in a series of temporal phases. The earliest, lasting several weeks, appears to include the clearance of phagocytosed particles via the bronchial tree. The terminal phases appear to be related to solubility at interstitial sites. While the mechanisms and dynamics of particle deposition and clearance are reasonably well established in broad outline, reliable quantitative data are lacking in many specific areas. More information is needed on: (1) normal behaviour, (2) the extent of the reserve capacity of the system to cope with occupational exposures, and (3) the role of compensatory changes in airway sizes and in secretory and transport rates in providing protection against occupational exposures, and in relation to the development and progression of dysfunction and disease.

Aerosols↗
PubMed1980

Age-dependent changes in prevalence, size and proliferation of arterial lesions in cockerels. I. Spontaneous lesions.

Age-dependent changes were determined in the prevalence, size and proliferation of early spontaneous aortic lesions in white leghorn cockerels. Groups of 6 animals received weekly intramuscular injections of dimethyl sulfoxide (DMSO) or remained uninjected. They were sacrificed at 6, 8, 12, 16, 20 and 38 weeks of age. Lesions were observed microscopically in all animals 8 weeks of age and older. They appeared in 20-30% of the aortic segments until 16 weeks of age and in 60% of the segments thereafter. The presence of a long single lesion along the aortic segments until 16 weeks of age and in 60% of the segments thereafter. The presence of a long single lesion along the aortic length was revealed by sectioning serially, at 50 micrometers intervals, 10-20 mm lengths of lesion-containing aorta. Between 8 and 20 weeks of age, lesion cross-sectional area increased by a factor of 2.4 while lesion volume index increased by a factor of 6. Similar patterns of proliferation were observed at each time point between lesion cells and those in the underlying media. Labeling indices of media and lesion cells were highest when the animals were growing rapidly and lowest when the animals reached full size. The results indicate that in the cockerel: (1) spontaneous lesions increase in depth and extend radially at a low constant level between 8 and 20 weeks of age and increase markedly in length between 16 and 20 weeks, (2) lesion cell proliferation is sufficient to account for the observed increase in lesion size, and (3) proliferation of lesion cells and medial cells may be governed by the same control mechanism(s).

Aging↗
PubMed1980

Inhalation carcinogenesis by dimethylcarbamoyl chloride in Syrian golden hamsters.

The comparative carcinogenicity of dimethylcarbamoyl chloride (DMCC) was studies in male, Syrian Golden Hamsters by inhalation. Hamsters were exposed to 1ppm and the exposure periods were 6 hours per day, 5 days per week for the lifetime of the animals. Fifty-one percent of the hamsters developed carcinomas of the nasal tract. Morphologically, all of these tumors were classified as squamous cell carcinomas. In comparing the response of rats and hamsters at 1 ppm DMCC, the rat seems to show increased sensitivity and the percentage of tumor yield is almost doubled, with the tumors appearing much earlier in rats than in hamsters. However, the remarkable tumor yield in both species indicates the potent carcinogenic effects of DMCC.

Animals↗
PubMed1979

Approaches to the formulation of standards for carcinogenic substances in the environment.

After having agreed that standards are necessary for carcinogens that cannot be completely eliminated from the environment, two exchange groups in the U.S.S.R.-U.S. Cooperative present their different approaches to the problem. The Russian groups has recommended a benzypyrene standard of 0.1 microgram/100m3 of atmospheric air over populated regions and gives its experimental basis and theoretical rationale in the first part of this joint paper. Lifetime experiments in adult rats over a wide range of dose levels permit the determination of a largest ineffective dose level with respect the theoretical time of first tumor as well as incidence. The standard is set by extrapolation based on body weight and uses a safety factor of 10 to account for the additional susceptibility in embryogenesis and childhood. The U. S. group presents a mathematical model of time-to-tumor occurrence which permits the prediction of population incidence and life span shortening from time-to-tumor data in animals or man. It assumes the distribution of mortality-corrected time to tumor is lognormal with the nth power of time inversely proportional to dose and with dose independence of the variability of the logarithm of time to tumor. The prediction is made by combining this distribution, fitted to the data, with population mortality tables. Both groups emphasize that substantial research efforts are necessary to improve the scientific basis for setting standards.

Animals↗
PubMed1979

A case-control study of hair dye use and breast cancer.

A case-control study of the relationship between hair dye use and breast cancer included 129 breast cancer patients and 193 control women drawn from the records of a multiphasic screening clinic. Information was obtained by telephone interview on a number of risk factors for breast cancer and on variables pertaining to hair dye use: chronologic time, duration, frequency, type, and color. From this, quantitative measures of cumulative hair dye use at various intervals prior to breast cancer (or an equivalent for controls) were obtained. A multivariate risk factor score was used to control for confounding variables. The adjusted relative risks for breast cancer versus hair dye use were greater than unity but were not generally significant. However, integral measures of hair dye use (No. of yr times frequency per yr) were significantly related to breast cancer when confounding variables were controlled. The association between hair dye use and breast cancer was greatest among women over 50 years of age and among those at lower natural risk for breast cancer. An analysis of temporal patterns showed that breast cancer was related mainly to hair dye use 10 or more years before cancer diagnosis. Because of the retrospective nature of the hair dye data and the small sample size, these results require further validation.

Adult↗