Low shear rate viscosity of fresh blood.
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Biomedical subjects
Publications and source records attributed to M Litt.
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In eukaryotes, the levels of specific tRNAs are closely correlated with the demands for their cognate amino acids in protein synthesis. To account for this phenomenon, we have proposed that the extent of aminoacylation of a given tRNA species in vivo controls the relative rate of synthesis or turnover of that species. Previously, we reported that Friend leukemia cells respond to histidine deprivation by increasing their relative level of tRNAHis by as much as two-fold, with no change in the relative level of tRNALeu. In this paper, we show that deprivation of leucine or tryptophan also causes a specific increase in the relative level of tRNAs cognate to the deprived amino acid. At least in the case of tRNATrp, the increases in relative tRNA levels are preceded by extensive declines in the steady-state extent of aminoacylation of the tRNA in vitro. We also find that different isoacceptors may respond differently to amino acid deprivation. These results suggest that decreased extents of aminoacylation of a given tRNA species in vivo cause increases in the relative rate of synthesis or decreases in the relative rate of degradation of that species.
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Mucus viscoelasticity on individual samples obtained from patients using combination oral contraceptives was quantitated by microrheometry. These results, in conjunction with mucus chemical characterization, indicate that combination oral contraceptive use eliminates the cyclic variations in mucus chemical, physicochemical, and rheologic properties associated with the ovulatory menstrual cycle. A correlation was demonstrated between the mucus elastic modulus and mucus nondialyzable dry weight, and the mucins produced during oral contraceptive therapy were shown to be similar to those recovered from ovulatory donors. Differences in mucus properties were noted when donors using estrogenic contraceptives were contrasted with those using androgenic contraceptives. On the basis of established relationships between sperm penetrability and mucus solids content, it was concluded that the use of contraceptives, as examined in this study, provided a secondary degree of fertility control at the cervical level.
Friend leukemia cells incubated with sublethal concentrations of histidinol for 5 to 6 days show up to twofold increases in their relative concentrations of histidine transfer RNA and no change in the relative concentrations of leucine transfer RNA. A similar effect is seen when cells are grown to stationary phase in the presence of 0.2 times the amount of histidine in Eagle's minimum essential medium. These observations support the theory that the concentrations of specific transfer RNA's are regulated by a mechanism that is sensitive to the extent of their aminoacylation.
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Middle ear effusions were collected from 10 patients (14 ears) with secretory otitis media. Mucoid samples were pooled and reconstituted to various concentrations of nondialyzable solids. Viscoelasticity was studied using a magnetic microrheometer and compared with mucociliary transport rates measured on the frog palate. Results indicate that the viscoelastic properties of middle ear mucus correlate with mucociliary transport. A transport maximum was found at a 2% nondialyzable solids content. Implications relative to ineffective mucociliary transport in secretory otitis media are discussed.
Quantitative viscoelastic and sperm penetration measurements were made on individual human cervial mucus samples collected from several ovulatory menstrual cycles. An inverse relationship was found to exist between these two mucus properties, with peak penetrability seen during the ovulatory phase of the cycle when viscoelasticity was lowest. Limited sperm penetration was also observed with follicular phase mucus. When mucus was collected three times daily, the first sample of the day showed reduced pH values and elevated percentage of nondialyzable solids (NDS) and viscoelastcity. Rates of mucus production were calculated for two cycles; the highest rate was seen during the ovulatory phase, with the follicular and luteal phases showing approximately 50% and 30% of this rate, respectively. Limited disparities were noted between midcycle changes in percentage of mucus NDS and viscoelasticity and in blood levels of total estrogens.
The familial aggregation of chronic bronchitis and obstructive airways disease was investigated in a propositus population of 430 persons aged 45-54 years and 1340 of their first (1 degree), second (2degrees) and third (3 degrees ) order relatives. All subjects were screened in their homes using a modified British MRC respiratory disease questionnaire and a portable spirometer. 1 degree relatives of propositi with either chronic bronchitis or obstructive airways disease demonstrated up to a two-fold excess prevalence of chronic bronchitis when compared to 1 degree relatives of non-affected propositi. This excess prevalence of chronic bronchitis was independent of sex, cigarette smoking patterns, respiratory illness history, residence in a common household, geographical distribution within the study community and the presence of alpha1-antitrypsin Pi variants. The prevalence of chronic bronchitis in 1 degree relatives of diseased propositi was also greater than in 2 degrees relatives of diseased propositi, in whom the prevalence approximated that of the general population.
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Tracheal mucociliary clearance studies, mucus collections, and rheologic studies were performed on a weekly basis in 7 adult purebred beagles in an attempt to correlate clearance rate with rheology of mucus. Clearance rates were determined by a percutaneous transtracheal, radioisotope injection technique. Mucus was collected from dogs equipped with a tracheal pouch, and rheologic determinations were performed on a dynamic microrheometer. Individual analysis of data for each dog failed to reveal any significant relationship between clearance rate and any parameter of elasticity or viscosity. However, when data from all 7 dogs were pooled, covering a much wider range of the measured variables, it was seen that as the elastic modulus increased, the rate of clearance decreased. The mucociliary clearance rate was halved by an approximate ten-fold increase in elastic modulus of mucus.
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Histidinol is known to cause deacylation of histidyl-tRNA in cultured mammalian cells, thereby producing a functional deprivation of histidine. Such deprivation of an essential amino acid is known to produce various effects, including inhibition of tRNA synthesis and of nucleolar RNA synthesis and processing. It has been proposed [Grummt, F. & Grummt, I. (1976) Eur. J. Biochem. 64, 307-312] that this response to amino acid deprivation is mediated by decreases in GTP and ATP pool sizes caused by a deacylated-tRNA-dependent hydrolysis of GTP. In contrast, we find that Friend leukemia cells treated with histidinol show no significant changes in GTP or ATP pool sizes, although this treatment does produce the expected inhibition of rRNA and tRNA synthesis.
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Quantitative viscoelasticity measurements were made on individual human cervical mucus samples by microrheometry. Increases in mean values for mucus spinnbarkeit, ferning, and wet weight were associated with the ovulatory phase of the menstrual cycle, while no significant differences versus time were noted for mean values for sample pH or nondialyzable dry weight. A nadir in mucus nondialyzable solids (NDS) concentration and in visoelasticity was seen at or near midcycle. Substantial, highly reproducible, variations in mucus viscoelasticity were observed when mucus from different donors was compared. When the contribution of (NDS) to viscoelasticity was minimized by data normalization or by sample reconstitution, a significant increase in viscoelasticity was associated with the ovulatory phase of the cycle, suggesting the occurrence of a relative increase in mucin concentration or a compositional change in the mucus.
Several common mucolytic agents were screened for their ability to solubilize cervical mucus without incurring irreversible losses in mucus viscoelasticity. Sodium thiocyanate was selected on the basis of its effectiveness and handling convenience, and solubilized mucus was fractionated by gel filtration on Sepharose columns. The excluded mucin fraction was characterized by a high neutral hexose to protein ratio and contained all of the elasticity of thiocyanate-treated whole mucus. The concentration of mucin in individual mucus samples collected throughout the ovulatory menstrual cycle was determined from column elution profiles. An increased relative amount of mucin was associated with samples collected during the ovulatory phase of the cycle, and a strong correlation was obtained when the percentage of mucin in individual samples was plotted against their respective storage moduli. These results indicate that the cyclic fluctuations in mucus viscoelasticity seen previously at constant concentrations of nondialyzable solids can be attributed to variations in mucin concentration. Evidence was also obtained, however, for compositional differences in mucus derived from different patients.
Tracheal mucociliary clearance was studied by a radioisotope technique in pentothal-anesthetized beagles in the control, atropinized, or dehydrated state. Mucus collected from a tracheal pouch in each dog was used for in vitro bullfrog (Rana cantesbiana) palate clearance studies and compared to the in vivo clearance rates. In all three experimental states, there was a significant correlation between in vivo and in vitro rates, suggesting that tracheal pouch mucus is a good model for investigating the mucociliary flow properties of intact airway mucus. When compared to matched controls, atropine appeared to cause a slowing of the in vivo clearance rate but not of the in vitro rate. Dehydration had no effect on either. The appropriateness of the frog palate method in the study of human respiratory disease (e.g., chronic bronchitis, cystic fibrosis) as well as its potential as an objective method of assessing the effects of various therapeutic modalities in these diseases is discussed.
The viscoelastic properties of reconstituted canine tracheal mucus were correlated with the ciliary transport rate measured on the bullfrog palate. A maximum in mucociliary transport rate was found at an optimal concentration of nondialyzable solids of 1.5 to 2 per cent. At concentrations less than this value, the mucus had little or no elasticity and low rates of transport; at concentrations greater than the optimum, however, further increases in elastic modulus also resulted in decreasing transport.