Quantitative Comparative Studies Research Articles

Practicalities of localization in animal and human tumours

Factors affecting the selection and application of localization methods for measuring tumours by NMR spectroscopy are considered, with particular regard to the S/N ratio and to contaminating signal from outside the volume of interest. Methods of assessing the performance of localization techniques are considered, and their importance for quantitative measurements and comparative studies is discussed.

Application of normative calculations in quantitative comparative mineralogical studies of bauxite

A CIPW-derived petrochemical calculation procedure is proposed in this paper for the conversion of whole-rock chemical analyses of bauxites and related materials into normative mineralogical suites. This method is based on the use of normative chemical formulas on a weight percentage basis using eight oxides and hydroxides, five residual and secondary silicates, amorphous silica and quartz.

Geochemistry of the Trans-Labrador granitoid belt, Canada. A quantitative comparative study of a Proterozoic batholith and possible Phanerozoic counterparts

Abstract The Trans-Labrador granitoid belt (TLGB) of eastern Canada is a 600 km-long magmatic province, that forms part of a wider belt of Lower to Middle Proterozoic crust along the southern margin of the pre-1800 Ma cratonic nucleus of North America. The size, geometry and tectonic position of the TLGB invite comparison with continental margin batholiths such as those of circum-Pacific areas. Quantitative comparative studies using a large, statistically representative, database suggest that there are significant contrasts between the compositional spectra and differentiation trends of the TLGB and typical continental arc batholiths. Specifically, the TLGB is dominated volumetrically by alkali-calcic granites (s.s.), showing locally agpaitic tendencies and relatively enhanced levels of F, Zr and REE. Such trace element characteristics invite comparison with “A-type”, “anorogenic” or “within-plate” granites, and some components of the TLGB fall into this category. In terms of bulk compositional spectra, the TLGB is similar empirically to post-tectonic and anorogenic intrusions of the Newfoundland Appalachians. It is suggested that a continental arc setting is inappropriate for the TLGB, and that a more likely environment is a post-orogenic setting dominated by crustal thickening, uplift and transcurrent faults. It is also possible, however, that the TLGB was generated in an intraplate environment by melting and vertical differentiation of continental crust in response to thermal input from the mantle. It is suggested that the use of large, representative databases, coupled with quantitative comparative studies of compositional spectra and differentiation trends, may be a useful approach in the discrimination of batholiths from different tectonic environments. At the present time, however, studies of this type are hampered by the lack of representative data from “type” areas.

Quantitative studies of inhibitors of ADP-ribosylation in vitro and in vivo

The ADP-ribosyl moiety of NAD+ is consumed in reactions catalyzed by three classes of enzymes: poly(ADP-ribose) polymerase, protein mono(ADP-ribosyl)transferases, and NAD+ glycohydrolases. In this study, we have evaluated the selectivity of compounds originally identified as inhibitors of poly(ADP-ribose) polymerase on members of the three classes of enzymes. The 50% inhibitory concentration (IC50) of more than 20 compounds was determined in vitro for both poly(ADP-ribose) polymerase and mono(ADP-ribosyl)transferase A in an assay containing 300 microM NAD+. Of the compounds tested, benzamide was the most potent inhibitor of poly(ADP-ribose) polymerase with an IC50 of 3.3 microM. The IC50 for benzamide for mono(ADP-ribosyl)transferase A was 4.1 mM, and similar values were observed for four additional cellular mono(ADP-ribosyl)transferases. The IC50 for NAD+ glycohydrolase for benzamide was approximately 40 mM. For seven of the best inhibitors, inhibition of poly(ADP-ribose) polymerase in intact C3H1OT1/2 cells was studied as a function of the inhibitor concentration of the culture medium, and the concentration for 50% inhibition (culture medium IC50) was determined. Culture medium IC50 values for benzamide and its derivatives were very similar to in vitro IC50 values. For other inhibitors, such as nicotinamide, 5-methyl-nicotinamide, and 5-bromodeoxyuridine, culture medium IC50 values were 3-5-fold higher than in vitro IC50 values. These results suggest that micromolar levels of the benzamides in the culture medium should allow selective inhibition of poly(ADP-ribose) metabolism in intact cells. Furthermore, comparative quantitative inhibition studies should prove useful for assigning the biological effects of these inhibitors as an effect on either poly(ADP-ribose) or mono(ADP-ribose) metabolism.

Insect diversity: facts, fiction and speculation*

Biologists are still trying to grasp the global dimensions of the phylum Arthropoda and its major class the Insecta, in spite of the fact that over a million species of arthropods have been described. The canopy of rain forest trees is believed by many to hold the key to the immense diversity of insects. In recent years the use of knock-down insecticides to sample insects from rain forest canopy has revealed information on the canopy’s arthropod inhabitants and community structure. The sampling techniques involved are outlined and data reviewed on taxonomic and guild structure, species abundance, body size and biomass ofinsects, and the faunal similarity of trees. Calculations by Erwin (1982), based on knock-down insecticide studies ofthe beetle fauna ofone species ofcentral American tree, suggest there may be 30 million species of tropical forest arthropods. Reanalysis of these calculations, using additional data, produces a range of possible estimates from about 10 to 80 million. The unknown range of plant host-specificities of tropical insects is the main weakness of this method of calculation. Assessment of the faunal importance of the canopy in relation to that of other rain forest biotopes requires comparative quantitative studies. The preliminary results of one such simple study suggest that over 42 million arthropods may be found in a hectare of Seram rain forest (at the time of study), and that 70% occur in the soil and leaf litter and 14% in the canopy. They also suggest that Collembola and Acarina are the dominant groups in this hectare, and that there are as many ants as all the other insects (excluding Collembola),

Comparative Quantitative Studies on Central and Peripheral α-Adrenoceptors

Clonidine and related drugs are known to be α-adrenoceptor agonists. This agonism may occur at the level of at least four distinctly different populations of α-adrenoceptors, leading to the overall effects of hypotension and bradycardia (Fig 1). The following proposed effects should be distinguished: (1) The stimulation of both and α2-adrenoceptor subtypes at postsynaptic sites in vascular smooth muscle causes vasoconstriction and, hence, a pressor response. (2) The stimulation of central α2-adrenoceptors in the brain stem induces hypotension and bradycardia mediated via central mechanisms. (3) The stimulation of presynaptically located α2-adrenoceptors in the heart may contribute to the overall bradycardia.

Comparative Quantitative Studies on Central and Peripheral α-Adrenoceptors

Comparative Quantitative Studies on Central and Peripheral α-Adrenoceptors

Quantitative Comparative Studies on Peripheral and Central Bradycardia Induced by Imidazolidines

AbstractCentral hypotensive activity of α‐adrenoceptor agonists generally parallels bradycardic potency. This has led to the conclusion that bradycardia, like the induction of hypotension, is also initiated within the central nervous system by stimulation of α2‐adrenoceptors. However, bradycardia has still been found for a very hydrophilic α‐adrenoceptor agonist not showing central hypotensive activity following systemic application. In view of this inconsistency quantitative comparisons were made between central hypotensive activity and overall bradycardic potency in anaesthetized normotensive rats after intravenous administration within a series of phenyliminoimidazolidines. The log dose‐bradycardic response curves of the more lipophilic derivatives were monophasic, whereas those of the hydrophilic compounds were characterized by a bisigmoidal shape. As a result of the dual nature of this effect, the potency of the drugs to decrease heart rate was quantified at 10%, pC10(HR), as well as at 20%, pC20(HR), effect level. Linear regression analysis showed a highly significant correlation between pC20(HR) and hypotensive activity. Lipophilicity, log P′, had to be added to verify this relationship for pC10(HR). For the latter variable, however, a linear relationship was derived with the potency of the compounds to inhibit cardiac frequency via stimulation of presynaptic α2‐adrenoceptors in the heart itself. These results strongly suggest that overall bradycardia of α‐adrenoceptor agonists may consist of a peripheral and a central component. Both mechanisms are governed by the stimulation of α2‐adrenoceptors. The peripheral mechanism (presynaptic cardiac α2‐adrenoceptors) is triggered by hydrophilic as well as lipophilic compounds following systemic application. The induction of central bradycardia (central α2‐adrenoceptors) and hypotension is but limited to the more lipophilic drugs.

Protein kinase activity and substrates at the surface of intact HeLa cells.

Evidence is presented for the location at the surface of HeLa cells of a protein kinase capable of phosphorylating surface as well as extracellular (foreign) proteins. The reaction products have been found to be proteins containing phosphoryl groups as monoesters of seryl and threonyl residues (but not of tyrosine). The enzyme is of the cyclic AMP-independent type, since neither cyclic AMP nor the heat- and acid-stable inhibitor protein (specific for cyclic AMP-dependent protein kinases) influenced its activity. Further, co-substrate ATP could in part be substituted by GTP, and the spectrum of proteins phosphorylated by the ecto-enzyme differed from that phosphorylated by cyclic AMP-dependent protein kinases. Evidence for the ecto-enzymic nature of this protein kinase includes (a) utilization of co-substrate and location of products at the surface of cells carefully controlled as being in an intact state and (b) phosphorylation of exogenous protein (phosvitin; specific serum proteins) by intact cells. Conclusive proof was gained by qualitative and quantitative comparative studies of phosphorylation in cultures with varying degrees of damaged cells either as a whole or after separation into groups of intact and damaged cells by electronic cell sorting. The results of experiments with cell sonicates excluded the possibility that either enzyme or substrates released from damaged cells were simply adsorbing to the cell surface.

Appreciation of the value of different bacterial test systems for detecting and for ranking chemical mutagens.

In more than thirty years of intensive research and development in the field of bacterial mutagenicity testing, a wide range of strains with various genetic endpoints has become available for routine studies. Selective genetic systems of great simplicity and handiness have been developed which assay for gene mutations, such as reversions from auxotrophy and forward mutations to antimetabolite resistance, lysogenic induction of prophages, and DNA repair. The introduction of techniques which take the mammalian metabolism into account, furthermore, makes bacterial systems potentially useful in (i) the primary identification of mutagens and non-mutagens and (ii) the quantification and ranking of relative mutagenic potency. For primary identification purposes, sensitive strains of Salmonella typhimurium LT2 and of Escherichia coli B and K-12 with altered DNA repair capacities have been constructed which demonstrate a high predictive value for many chemical mutagens (and carcinogens). Comparitive studies showed that techniques using these strains can be efficiently standardized and calibrated. Several classes of chemicals with known mutagenic properties, however, are still not detected, or underestimated, in using standard assay procedures. Examples are presented of such compounds, which can be efficiently detected as mutagens upon — slight — modifications of the experimental conditions or the DNA repair capacity of the tester strains. It appears, therefore, advisable to modify and adjust the standard testing protocol to the particular type of chemical under study and to thoroughly calibrate the system with appropriate mutagenic and non-mutagenic reference compounds. For the quantification of mutagenic potency, question remains whether bacterial systems will be of general usefulness. There are indications that the mutagenic activity of certain classes of chemicals, e.g., oxazaphosphorines, aflatoxins, nitroimidazoles, shows some proportionality with their chemical reactivity and that the relative degree of mutagenicity is similar in bacteria and in eukaryotic systems. The attractive possibility of employing in the quantification process those tester strains used for the primary identification appears, however, problematic, because (i) back mutation systems are rather specific in their response to certain mutagens and (ii) the use of strains with altered DNA repair and metabolism may lead to gross overestimations or underestimations of mutagenic potency in the corresponding wild types. More systematic studies are needed to determine the most representative genetic endpoints and genetic background under accurate determination of dose to the target molecule. The feasibility of such quantitative comparative studies has recently been demonstrated in a variety of organisms including bacteria, fungi, Drosophila, and mammalian cells in vitro and in vivo. Proposals are made to use in further comparative studies chemicals, such as procarbazine, cyclophosphamide, and ethylnitrosourea, for which data on gene mutation induction in germinal cells of mammals are available.

Thermal degradation of polymers. XXIII. Vacuum pyrolysis of poly(p-N,N-diethylaminostyrene); the products volatile at pyrolysis temperature, liquid or gaseous at room temperature

The products obtained on vacuum pyrolysis of poly(p-N,N-diethylaminostyrene) are described. The effect of sample molecular weight and pyrolysis temperature are compared with that observed for polystyrene degraded under identical conditions. The liquid products were separated using gas–liquid chromatography and identified using Kovat's retention index and mass spectrometry. Significant differences were found between the products arising from the two polymers which are discussed in terms of mechanisms involving N-alkyl and N-aryl bond scission and the subsequent reactions of the generated radicals. Comparative quantitative studies are described and discussed.

Collection of cytological specimens with a cell aspirator with reference to the wooden spatula method: II. Comparative quantitative and qualitative studies

This article describes the results of comparative quantitative and qualitative examinations of specimens obtained by testing 65 individuals by means of a cell aspirator and a wooden spatula. The studies were performed on a clinically normal mucosa as well as on different mucosal lesions. A statistical analysis of the cells obtained showed that the cell aspirator quantitatively produced significantly better results both with regard to the total number of cells obtained and to the number of epithelial cells in the different stages of maturity. The number of cells obtained turned out to be dependent on surface structure and the size of the lesion, however, Qualitatively the cell aspirator collected epithelial cells which were better preserved morphologically, but also a larger number of compact cell clusters. The number of erythrocytes was low. The structure of these blood cells was well preserved, indicating bleeding arising in connection with the taking of the specimens. The number of leucocytes was larger in the aspirated material. The degrees of fixation and staining were similar. The authors make recommendations for using the cell aspirator in such a manner as to obtain the best qualitative results.

QUANTITATIVE STUDIES OF THE RENAL CORPUSCLES III:

Comparative quantitative studies of glomeruli in biopsies of the guenon monkey kidney were made to give a numerical measure of the effect of varying periods of fixation of the biopsy tissue in Carnoy's fluid (1-2-24 hrs.), and of the effect of progressive post mortem delay before renal tissue samples were taken (2-4-6-12 hrs.). Additional aims were to determine possible quantitative differences between subcapsular, intermediate and juxtamedullary glomeruli, and to determine whether the glomerular area should be determined with reference to the inner aspect of Bowman's capsule (total area) or to tangents laid at the top of the capillary loops (corrected total area). The quantitative methods used were total and differential counts of glomerular nuclei by light microscopy and point counting for determination of glomerular and mesangial areas. Statistical evaluation was made by a two-way analysis of variance. The differential counts of nuclei were not affected by duration of fixation, nor by post mortem delay up to 12 hrs. before tissue samples were taken. The mesangial area expressed as a percentage of total area was significantly lower two hours post mortem, while total nuclear concentration was significantly lower at time 0 and two hours post mortem than at four, six and 12 hours post mortem. Total nuclear concentration increased as duration of fixation was increased, probably a reflection of tissue shrinking. Differences in nuclear concentration were also noted at different levels of the renal cortex. These differences were only apparent when the glomerular area was determined with reference to the inner aspect of Bowman's capsule, and disappeared when the corrected total area was used. It is concluded that duration of tissue fixation and post mortem delay before tissue samples were taken both affect method sensitivity, as reflected by some, not all, of the parameters measured. The numerical differences in the parameters were not large, however, and it will be the specific study which will determine whether variable fixation times and post mortem delay in obtaining tissue samples is acceptable. As most renal biopsies contain both subcapsular and juxtamedullary glomeruli there is probably no advantage in using the corrected glomerular area instead of the total glomerular area limited by Bowman's capsule.

Changes in Blood Proteins of Deer during Gestation and Suckling

Quantitation of total serum proteins (TSP), albumin, and alpha-, beta-, and gamma-globulins was done for 22 white-tailed deer (Odocoileus virginianus): 7 pregnant does having 11 fetuses during 115-194 days gestation, and 2 pairs of twin male fawns from birth to 24 days of age (one pair was allowed [N+] and the other not allowed [N-] to suckle their dams). During gestation, mean TSP were approximately 54 and 30 mg/ml of serum in does and fetuses, respectively; TSP, albumin, and alphaglobulin of does tended to decrease during gestation but beta-globulin tended to increase. Does' gammaglobulin decreased significantly with gestation time. Fetal alphaand beta-globulin remained relatively constant throughout gestation, but fetal TSP and albumin tended to increase during gestation. Mean TSP in neonatal deer were 55.0 and 37.7 mg/ml for N+ and Nfawns, respectively. Corresponding respective values for albumin, alpha-globulin, and beta-globulin were 27.8 and 22.9, 6.3 and 7.2, and 8.5 and 15.2 mg/ml of serum. Gamma-globulin was absent from Nfawns. Mean gamma-globulin in N+ fawns was 12.3 mg/ml; it decreased exponentially from 26.6 mg/ml on day 1 to 2.9 mg/ml on day 24 and exhibited a half-life of approximately 13 days. J. WILDL. MANAGE. 39(2):346-354 The serum proteins have been studied in many animal species, and comparative qualitative and quantitative studies of these proteins have been done in adult animals. A study of the blood proteins of the adult white-tailed deer and the natural variation of blood proteins in this wild ruminant recently was presented by Miller et al. (1965). The serum proteins of fetuses and young growing animals also have been studied, and an excellent review has appeared (Kekwick 1959). For the white-tailed deer, an investigation of the blood composition of nursing deer fawns and the milk and blood of their dams was conducted by workers in Michigan (Youatt et al. 1965). Polymorphism was found to exist in the postalbumin portion of fawn serum protein (Seal and Erickson 1969). Polymorphisms in the hemoglobin of adult and juvenile white-tailed deer also were reported in the same paper. Detectable quantities of serum immunoproteins were shown to have been synthesized in the bovine fetus rather than to have c ossed the placenta (Miller and Hubbert 1972). However, this fetal biosynthesis was also shown to be nonsignificant quantitatively (Trevorrow and Washburn 1970). The principal part of immunoproteins found in the young animal, therefore, was either transferred in utero to the fetus or was absorbed from the colostrum. The type of placentation dictates whether the principal avenue is the in utero route. Multilayered syndesmochorial placentation in the deer (Harrison and Hamilton 1952), as in the sheep, dictates the principal avenue of absorption of immunoproteins in both species to be from the colostrum. Quantitation of changes in composition of blood proteins of the dam and fetus done longitudinally with gestation has not been reported, to our knowledge. Changes in 1 Authorizxed by the Director of the Pennsylvania Agricultural Experiment Station for publication as Paper No. 4275 in the journal series. 'Present address: Virginia Cooperative Wildlife Research Unit, Virginia Polytechnic Institute and State University, Blacksburg 24061. 346 J. Wildl. Manage. 39(2):1975 This content downloaded from 207.46.13.131 on Sat, 15 Oct 2016 04:16:53 UTC All use subject to http://about.jstor.org/terms BLOOD PROTEINS OF DEER * Hartsook et al. 347 concentration of plasma proteins of the fetal calf were reported by Baetz et al. (1971). Therefore, one purpose of this report was to provide data on blood protein changes for the dam and fetus of the white-tailed deer during the latter period of gestation. Changes with time in the concentration of serum proteins of normal deer fawns suckling their dams have been presented by Tumbleson et al. (1970). A second purpose of this report was to compare, qualitatively and quantitatively, the blood proteins of deer fawns either allowed or not allowed to suckle their dams from birth through 24 days of age. We wish to thank P. Briggs for assistance with electrophoretic separations and quantitations. MATERIALS AND METHODS

Roadrunners: activity of captive individuals.

Two roadrunners, Geococcyx californianus, readily accepted an activity wheel as an outlet for locomotor activity. The birds were strictly diurnal and tended to be most active per unit of time in the predusk hours. There was less activity on partly overcast days than on clear days. Dim light and darkness were strongly inhibitory, even during daytime hours; bright light was stimulatory, even during nighttime hours. These findings appear to open the way for quantitative comparative studies of the influences of environmental factors on the activity of cursorial birds.

Substitutes for the Mycobacteria in Freund's Adjuvants in the Production of Experimental “Allergic” Encephalomyelitis in the Guinea Pig

Summary Experimental “allergic” encephalomyelitis (EAE) can be readily induced in guinea pigs by the single intracutaneous injection of neural tissue and Freund's “complete adjuvants” (killed mycobacteria in water-in-oil emulsion). Quantitative comparative studies have revealed that many other acid-fast organisms are equally effective, that Gram-negative organisms are effective but require about ten times as much to produce comparable degrees of EAE, and that Gram-positive organisms are relatively ineffective. Exceptions to this pattern are recognized, but the pattern suggested that organisms rich in capsular lipids and therefore lipophilic were more effective partly because of this surfacetension phenomenon and partly because of the presence of lipopolysaccharide (LPS). Both of these hypotheses were tested, the first by siliconizing ineffective Gram-positive organisms, and the second by testing commercially available LPS from Salmonella typhosa. Although at the moment apparently mutually contradictory since LPS forms an aqueous colloid, the results were according to prediction and indicate that physical as well as chemical aspects of adjuvants must be considered in an attempt to understand the mechanism of action of immunologic adjuvants.

Immunochemical characteristics of cannine serum albumin in ontogenesis

Qualitative and quantitative comparative immunochemical studies have been made of the serum albumins of fetuses, puppies, and adult dogs, using Ouchterlony's diffusion method, and immunoelectrophoresis according to Grabar; Heidelberger's curve was used in evaluation of quantitative results. The albumins were isolated by starch slab electrophoresis.

A cross-cultural approach to mental health problems.

There are many ways of viewing the etiology of mental disease. It can be understood as being due to heredity, due to fixation at infantile levels of instinctual development and faulty early object relationships, due to biological dysfunctions and due to influences arising from interpersonal relationships within the society or culture in which an individual lives. None of these viewpoints is "wrong" but each represents a segmental view of a multilateral process. In the foregoing an attempt has been made to survey our present knowledge regarding the relevance of social and cultural factors to the etiology and treatment of mental illness. In this survey which inevitably had to be incomplete many questions have been raised and few have been answered. It has been shown that the major categories of mental disorders occur ubiquitously, that there is some evidence that they are distributed unevenly, that nosological differences exist between different cultural areas and that differences both in frequency and in nature of clinical manifestations can be related to cultural differences. Methodological difficulties especially of comparative quantitative studies but also of qualitative studies have been pointed out.

NUTRITIONAL STUDIES ON THE GENUS HIRSUTELLA: I. GROWTH RESPONSE IN AN ENRICHED LIQUID MEDIUM

Quantitative comparative studies on the growth of Hirsutella gigantea in shaken yeast extract – dextrose medium have shown that the rate of growth and total yield is affected by the quantity of inoculum. The highest yield is obtained with an inoculum level ranging from 0.2 to 0.4 mg/50 ml; moreover results from repeated experiments tend to be relatively uniform. With smaller quantities of inoculum, i.e. 0.1 mg or less, the uniformity of growth among replicates is affected. An increase in the amount of inoculum above the optimum, while accompanied by a higher rate of growth, results in a gradual decrease in the total yield.With approximately 0.2 mg of inoculum the maximum yield, 673.4 mg of fungal mycelium, was obtained after 12 days' incubation in a medium containing 1.5% yeast extract and 2% dextrose.The fungus does not grow in a basal dextrose–salts medium with potassium nitrate or ammonium nitrate as the nitrogen source. The effectiveness of yeast extract indicates a requirement for organic nitrogen. Yeast extract may also act as a source of growth factors.

Transfer of Specific Blood Serum Proteins to Lacteal Secretions near Parturition

Summary Comparative quantitative electrophoretic studies were made of the specific protein components present in the lacteal secretions of heifers and dry and milked cows near parturition. Near parturition, the relative concentration of the specific proteins synthesized in the mammary gland decreased with a corresponding increase of protein components entering from the blood. Small amounts of all of the major blood protein components were detected in the secretions; however, as parturition approached the levels of two immune globulin components with the same properties as the blood, β 2 -and γ 1 -globulins increased to tremendous levels. Calculations of the amount of β 2 - and γ 1 -globulins leaving the blood indicated that they quantitatively accounted for the immune globulin components appearing in the lacteal secretions.