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PubMed1979

Potential antitumor agents. 29. Quantitative structure-activity relationships for the antileukemic bisquaternary ammonium heterocycles.

Quantitative relationships between physicochemical drug properties and antileukemic (L1210) efficacy have been examined for a series of bisquaternary ammonium heterocycles employing multiple variable regression analysis. Three measures of biologic response were examined: ILSmax, the percentage increase in mean life span of leukemic animals at the LD10 dose; D40, the drug dose necessary to provide 40% increase in life span; and CI (=LD 10/D40), the chemotherapeutic index. A cross correlation matrix between these three measures and the LD10 values demonstrates ILSmax and CI to be independent of toxicity. D40 is highly inversely correlated with LD10 and positively correlated with ILSmax, suggesting that this parameter measures a composite of both drug selectivity and toxicity. Superior regression equations resulted at all stages employing ILSmax as a measure of antitumor selectivity. Acceptable equations modeling LD10 could not be obtained. There was a parabolic relationship between agent lipophilic-hydrophilic balance, measured as chromatographic Rm values, and ILSmax. To reduce residual variance in the L1210 screening data, not accepted by this parabolic equation, measures of agent-DNA interaction were investigated as possible indices of site fit. Relative levels of drug-DNA interaction were obtained by spectrofluorimetric quantitation of drug displacement of DNA-bound ethidium. Addition to regression equations of agent C50 values for calf thymus DNA, those micromolar drug concentrations necessary to displace 50% of the ethidium bound to that DNA, provided a significant reduction in the screening data variance. C50 values for drug interactions with poly[d(A-T)] and poly[d(G-C)] were also investigated as possible indicators of drug selectivity towards different DNA sites. Marked differences were observed in the C50 values for the two synthetic nucleic acids, with those for calf thymus DNA and poly[d(G-C)] proving highly covariant. A regression equation containing a positive term in C50[poly[d(G-C)]] and a negative term in C50-[poly[d(A-T)]] provided the greatest acceptance of the variation in the biologic data. The term in C50[poly[d(A-T)]] is the single most important equation term, alone accounting for 35% of the variance in the data. This best equation provides both an adequate summary of the L1210 screening data for the 174 active compounds considered and a physical explanation for the antitumor selectivity for these agents. The major factor influencing antitumor selectivity in these drugs is their ability to distinguish alternating adenine-thymine sequences in DNA.

Animals↗

PubMed1975

Physical therapist assistant selection and academic success.

Assessment of a standardized test as one criterion for student admission to a physical therapist assistant program is made. Comparisons are made of ACT scores between the physical therapist assistant and associate degree nurse, and the physical therapist assistant and the practical nurse. A correlation matrix was used to analyze data with differences among the three groups determined by t test computation. This sample supports a positive correlation of ACT test scores with graduation grade point average. The means show no significant difference between the two associate degree programs and a significant difference between the associate degree programs and the practical nurse program.

Achievement↗

PubMed1977

Relation of food consumption to cancer mortality in Japan, with special reference to international figures.

The present study was designed to examine the epidemiological association of food consumption with cancer mortality in Japan, if any, in comparison with similar examinations in developed countries including Japan, in a search for dietary factors in cancer etiology. Whereas food consumption patterns in Japan was believed to be specific among developed countries, this study revealed that the correlation matrix among major foods both for international and Japanese data made it possible to categorize these foods into two groups with some similar patterns, since there should be observed a positive or negative correlation for each pair of foods. The patterns for correlation of food consumption to cancer mortality in Japan were found to be considerably different from those in developed countries, and this suggested that the epidemiological association between the two in Japan, if any, could be specifically evaluated from that in develop countries. The urban-type region for food consumption in Japan, however, indicated a possible westernization for the relation of food consumption to cancer mortality as well as for food consumption patterns, whereas the traditional Japanese region for food consumption did not indicate any similarity with westernization for the relationship between food consumption and cancer mortality, as well as for food consumption patterns. The above findings also suggested that there might be a possible significance for the regionalization of Japan in such studies, and that the urbanization of food consumption patterns in Japan would show that this country has a similar pattern of association between food consumption and cancer mortality as observed among developed countries in Europe and/or North America.

Dairy Products↗

PubMed1979

HLA--D typing with lymphoblastoid cell lines. IV. Allelic relationships.

Responses of approximately 200 persons were measured by mixed leukocyte cultures against 41 lymphoblastoid cell lines which were thought to be homozygous for HLA--D (i.e. LCL-HTCs). These responses were standardized by computer analysis and the resultant Interaction Indices for each LCL-HTC were compared with those of every other LCL-HTC in a correlation matrix of 861 independent analyses. Only those analyses involving LCL-HTCs of defined HLA--D types are reported here. In general, these studies confirmed many allelic relationships of reputedly similar LCL-HTCs; however, several unexpected groups of correlations suggested that groups Dw1 and 3 overlap to form Groups "1a-3," "1b-3" and "true 3." The "1b-3" group also included Dw8. Segregation of the "1b-3" allelic group was also observed in a family study. These preliminary analyses suggest a working model for further investigation of HLA--D allelic relationships (Fig. 3). On the other hand, they may also be interpreted to suggest that "typing" with LCL-HTCs may be controlled by a separate HLA locus which is closely related to, but distinct from, HLA--D.

Alleles↗

PubMed1978

Epidemiology of poly-parasitism. II. Types of combinations, relative frequency and associations of multiple infections.

Frequency distributions, including all of the observed types of combinations of multiple infections with different helminths and protozoa are presented for sample villages of the African Savannah and of the trans-Andean part of Peru. Measurements of correlation between these infections based on properties of the multivariate, multinomial distribution are calculated to show age and sex patterns of association in different population samples. A correlation matrix for combined infections with Dipetalonema perstans, D. streptocerca and Loa loa, in villages in the rain forest of Zaire indicates that there is a statistically significant association between the two species of Dipetalonema and L. loa. There is also a strong association between the numbers of the microfilariae of D. perstans and D. streptocerca in multiply infected individuals. This correlation is strong only in the rain forest; it is insignificant in the other ecological zones of Bas-Zaire included in the study. The data suggest that there may be selective host factors that influence the extent, distribution and the types of multiple infections in a community.

Adolescent↗

PubMedDate not supplied

Use of TLC and multivariate mathematical statistical methods to study the interaction of monoamine oxidase inhibitory drugs with amino acids.

The interaction of 17 monoamine oxidase inhibitory drugs (propargylamine derivatives) with amino acids was studied by charge-transfer chromatography. The data set was evaluated by principal component analysis (PCA). To assess the effect of the information loss caused by normalization, PCA was separately carried out on the covariance and on the correlation matrix. The strength and selectivity of interaction was separated by the spectral mapping technique. Calculation proved that the amino group of the drugs interacted with the second carboxyl group of dicarboxylic amino acids, and that the interaction was of electrostatic character. This finding made probable the direct interaction between the drugs and the target enzyme or enzymes. The results of both PCA methods were similar. However, coordinates of the spectral map showed only slight correlation with the corresponding coordinates of the two-dimensional nonlinear maps proving the different information content of the methods.

Amino Acids↗

PubMed1992

Glomerular changes in diabetes mellitus.

Ultrastructural, immunohistochemical and biochemical studies have improved our knowledge on the events occurring during the development of diabetic late complications. Immunohistochemical investigations of diabetic kidneys, using antibodies against various components of the extracellular matrix, showed increased collagen type IV (alpha 1,alpha 2-chain) deposition in the mesangial matrix, and a decrease of heparan sulphate proteoglycan in the mesangial matrix and glomerular basement membrane. Changes in matrix components seem to be the underlying cause of the alterations in renal function, as reflected by albuminuria and proteinuria. The occurrence of collagen type III in late diffuse glomerulosclerosis has been interpreted as an irreversible change in glomerular structure. The extent of alteration of the extracellular matrix correlates to a certain extent with the severity of nephropathy of the individual subject. The studies performed to date support the hypothesis that hyperglycaemia, whatever its origin, is the primary cause of diabetic late complications, although the pathobiochemical mechanisms are not yet fully understood. Increased intra- and extracellular levels of glucose and its derivatives are thought to contribute to diabetic tissue dysfunction. Three pathobiochemical theories are favoured in the current discussion: i) the polyol pathway ii) non-enzymatic glycation of proteins iii) direct influence of hyperglycaemia on the synthesis of matrix components. The evidence for the participation of the polyol pathway in the pathogenesis of diabetic nephropathy comes mainly from animal data using aldose reductase inhibitors, but only limited data are available for humans, so that the significance of this pathomechanism cannot yet be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1976

[Correlations between metric, cyto and histomorphological factors and thermographic findings in breast neoplasms].

Correlations between metric, cyto- and histomorphological characteristics and thermographical results of 119 carcinomas of the breast have been studied by statistical methods. For the purpose of semi-quantitative evaluation the chi2 of 14 characteristics were calculated from foursquare tables and summarized in a correlation matrix. The study revealed a significant increase of thermographically suspect pictures with increasing size, but this was independent of the depth (i.e. the distance from skin surface) of the tumors. The proportion of uncertain but not clearly suspect results was 35% with the infrared telethermovision method, in contrast to 8% with liquid crystal plate thermography. Thermographically non-suspect carcinomas (especially the negative cases with liquid crystal plate thermography) were rich in connective tissue or stroma in most cases. On the other hand, carcinomas with numerous mitoses, large cell nuclei, increased N/C-ratio and large and strongly stained nucleoli predominantly exhibited definitely suspect pictures. The significant correlation between number of mitoses, size and staining of nucleoli and the thermographic results emphasizes that, besides vascularization and altered thermo-regulatory functions, the metabolism of the tumor itself contributes to the temperature differences. The type of growth and histological grading indicate that tumors with unfavourable prognosis preferentially exhibit thermographically suspect results. The use of thermography as a screening method is restricted because of possible false negative results. On the other hand, its additional use is justified in view of the gain in information about the biological situation of suspect alterations of the breast.

Breast Neoplasms↗

PubMed1978

[EEG spectral analysis in normal children between the ages of 6 to 16. Choice and validation of the most significant parameters].

Numerous parameters have been proposed in order to describe the EEG power spectrum. Within the scope of an EEG study on the normal child between 6 and 16 years of age, the following problem had to be solved: given a group of 19 variables measured on 232 subjects in 5 situations, which of these variables best describe the population under examination. The algorithm proposed to answer this question is based on principal component analysis on the correlation matrix. Only 4 parameters are necessary to describe the EEG of a normal child of 6 to 16 years--these are Hjorth's parameters (activity, mobility and first order complexity) and alpha band power. They allow the observation of individual differences and the quantification for a given subject of the reaction to eyes opening, sensitivity to hyperventilation or even reactions that are difficult to perceive visually such as those resulting from doing arithmetic or vocabulary tests.

Adolescent↗

PubMed1992

Nature of romantic love in female adolescents.

In the present study, I intended to determine the similarity between Rubin's (1970) Love Scale components and five of Lee's (1976) six lovestyles in a relatively homogenous sample of 301 16- and 17-year-old British females. Items describing loving behaviors toward a particular individual were formulated to measure these lovestyles together with that of Ludus. The six orthogonal factors extracted from the correlation matrix of these and Rubin's items were called Love, Mutual Love, Respect, Similarity, Physical Attraction and Hostility. The results suggested that Rubin's Love Scale contained elements of Mania and Agape but none of Ludus, which could not be further differentiated. Rubin's (1970) Liking Scale, however, could be further subdivided into Respect (Pragma) and Similarity (Storge).

Adolescent↗

PubMed1978

Principles for identifying structural differences. Some methodological issues related to comparative factor analysis.

Several recent articles published in the Journal of Gerontology have been concerned with changes in factor structure of various psychological, social, and medical fitness measures. The present article reviews four principles for comparing structures and evaluates several recent articles in terms of these principles. The four principles are concerned with resolving: (1) problems of metric, (2) problems of rotation to similarity, (3) the number of factors problem, and (4) problems related to different extraction or rotational procedures across comparison groups. Utilization of a different metric in each correlation matrix implies that results may be a simple artifact of a different metric for each group. Failure to rotate to similarity and insufficient care with regard to the number of factors problem may result in artificially dissimilar structures. Finally, in comparing results across studies, differences in extraction or rotational procedures across different studies may result in differing results as artifacts of the methods employed.

Factor Analysis, Statistical↗

PubMed1976

Sex-differences in the agonistic behavior of spiny-mice (Acomys cahirinus).

Observations of 8 groups each containing three adult spiny mice (Acomys cahirinus) revealed that instances of chasing and physical displacement were quite common, while fighting and biting were rarely observed. The relationships between the most frequent behavioral categories were presented in a correlation matrix. In a second study, females tested in their home cages were dominant over males. In the males' home cages, however, no differences in the frequency of female vs. male aggression were observed. More instances of aggression were observed in the cages of the females than in the cages of the males.

Aggression↗

PubMed2026

Associations of genetically predicted interleukin-6 and tumor necrosis factor signaling pathways with mortality among persons with colorectal cancer: a two-sample Mendelian randomization.

BACKGROUND: Despite significant progress in identifying risk factors for colorectal cancer (CRC), factors influencing survival in people with CRC remain less understood. Pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been implicated in cancer progression and may influence CRC outcomes. We investigated associations between genetically predicted levels of IL-6 and TNF-α signaling pathways and mortality in people with CRC. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using cis-acting single nucleotide polymorphisms (SNPs) associated with soluble IL-6 receptor alpha (sIL6-RA) and IL-6 signal transducer gp130 (IL6ST), representing IL-6 signaling, and with TNF-α, and its soluble receptors (sTNF-R1, sTNF-R2). SNPs were obtained separately from two large genome-wide association studies (GWAS): deCODE and UK Biobank (UKB). The outcome was CRC-specific mortality among 16,964 CRC cases (4010 deaths) in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Analyses were stratified by tumor site and stage. The inverse variance weighted (IVW) method, incorporating a correlation matrix for dependent SNPs, was used for primary analyses. Because literature links TNF-α to CRC incidence, we additionally performed a simulation study to evaluate the potential impact of collider bias resulting from restricting analyses to CRC cases. RESULTS: Genetically predicted sIL6-RA was weakly positively associated with CRC-specific mortality (deCODE-SNPs (n = 13) HR per 1 SD increase: 1.06; 95% CI: 1.00-1.12; UKB-SNPs (n = 11) HR: 1.09; 95% CI: 1.02-1.17). Genetically proxied IL6ST levels showed no association with CRC-specific mortality in the overall sample (deCODE-SNPs (n = 19) HR: 1.04; 95% CI: 0.90-1.21; UKB-SNPs (n = 9) HR: 1.11; 95% CI: 0.87-2.42), while higher IL6ST levels were associated with increased mortality among patients with stage 2/3 disease (deCODE-SNPs (n = 19) HR: 1.45; 95% CI: 1.10-1.91; UKB-SNPs (n = 9) HR: 1.87; 95% CI: 1.22-2.89). No associations were observed for TNF-α, sTNF-R1, or sTNF-R2. Findings for all exposures were consistent across both GWAS datasets. Simulation analyses for TNF-α indicated collider bias was present but limited in magnitude. CONCLUSIONS: Our findings suggest that IL-6 signaling may play a role in CRC progression although of limited magnitude, whereas TNF-related pathways appear less relevant for prognosis.

Humans↗

PubMed1976

Addiction to diazepam.

Literature is reviewed which raises the question of diazepam's addicting potential. To explore this issue, 50 subjects referred from medical, surgical, and psychiatric clinics were evaluated by interview regarding their use of diazepam. Replies to a standardized interview were combined with physicians' ratings of addiction under two conditions: without and then with the knowledge that the drug in question was diazepam. A computer-aided analysis of these data, including a correlation matrix, revealed surprisingly strong evidence for diazepam's capacity to elicit tolerance and withdrawal in this sample. Psychiatric patients were no more "addiction-prone" in this regard than patients given diazepam for medical conditions. Of equal significance, physicians' impressions of addiction were significantly altered toward a more favorable view when they learned that the drug in question was diazepam. Implications for psychiatric and medical practice are discussed, and suggestions for further controlled research offered.

Administration, Oral↗

PubMed2026

Mapping Focal and Generalized Effects of Common Genetic Variants on Human Brain Structure.

Genome-wide association studies (GWAS) have advanced the quest to understand how specific genetic variants influence human brain structure and function. Recent work has identified hundreds of common variants associated with subcortical brain volumes, sparking interest in how these genetic markers overlap across brain networks. While this can be estimated by hierarchical clustering of the genetic correlation matrix to identify modular patterns of shared architecture, no brain-wide maps of these effects are available. To address this, we computed polygenic scores (PGS) from loci associated with ten brain volume regions of interest (ROIs): nine major subcortical structures and intracranial volume, with each locus weighted by its association with regional volume. In an independent sample from the discovery GWAS, we performed large-scale segmentation of 3D volumetric T1-weighted MRI scans using voxel-based morphometry (VBM) to map 3D profile of regions where gray matter volume (GMV) was associated with each PGS. We found statistically significant, localized effects for PGS defined for the amygdala, thalamus, and basal ganglia, but PGS for brainstem volume was associated with widespread differences throughout the brain. These brain-wide maps reveal patterns consistent with both localized and distributed genetic influences, offering a novel approach to interpret the genomic architecture of brain structure.

GWAS↗

PubMed1992

[Classification of congenital superior oblique palsy based on principal component analysis].

An attempt was to classify unilateral congenital superior oblique palsy principal component analysis. Each principal component was calculated by taking a linear combination of an eigenvector of the correlation matrix with a standardized original variable. The variables selected for the analysis were vertical deviation in the nine diagnostic positions of 51 cases measured by a synoptometer. The cumulative contributive percent of principal components showed that 88.5% of the variation were accounted for by the first three principal components. The first principal component accounted for 56.7% of the variation in samples indicating the extent of superior oblique palsy in which vertical deviation increases or decreases proportionately. The second principal component accounted for 20.6% of the variation of samples indicating the extent of the incomitance of vertical deviation with a vertical change of gaze. The third principal component accounted for 11.1% of the variation in the sample indicating the extent of the vertical deviation with a horizontal change of gaze.

Adolescent↗

PubMedDate not supplied

Statistical analysis of white blood cell data directed to the detection of malignancy in untreated patients.

A training set of 90 malignant cases (positives) and 61 non-malignant cases (negatives) was used to determine statistics for five parameters based on white blood cell analysis. The statistics used were thresholds, differences between the positive and negative means, and the weighted correlation matrix. Three decision methods using these statistics were then applied to a test set of 90 positives and 60 negatives. The percentage of correct decisions ranged from 98.67 per cent for parameter 3. The best result using only parameters capable of recognition by an automated apparatus was 94.00 per cent.

Cytodiagnosis↗

PubMed1979

Q factor analysis applied to describe attitudes toward dental care.

This study used a modified form of Q factor analysis to introduce students to methods to identify and describe patient and provider attitudes toward dental care. Factor analysis of questionnaire results and a person by person correlation matrix allowed students to compare their own attitudes with those of their patients, faculty, and significant people in their lives. Results indicate certain issues regarding dental care on which all subjects agree. Subjects grouped themselves along different factors according to the relative importance each issue had for them. By identifying these issues and groupings, students had a systematic description of their specific "dentist-patient relationship." By including clusters of people significant in their own lives, students became personally involved in the purpose, methods, and results of the analysis.

Attitude↗